Compound inhibiting in vivo phosphorus transport and medicine containing the same

ABSTRACT

An objective of the present invention is to provide compounds that can effectively suppress the concentration of phosphorus in serum to effectively prevent or treat diseases induced by an increase in concentration of phosphate in serum. The compounds according to the present invention are compounds represented by formula (I) and pharmaceutically acceptable salts and solvates thereof: 
     
       
         
         
             
             
         
       
     
     wherein A represents an optionally substituted five- to nine-membered unsaturated carbocyclic moiety or a five- to nine-membered unsaturated heterocyclic moiety, and   represents a single bond or a double bond, R 5  represents optionally substituted aryl or the like, Z represents —N═CHR 6 R 7  or the like, R 6  and R 7  represent H, optionally substituted alkyl, optionally substituted aryl or the like, R 101  and R 102  together form ═O, and R 103  and R 104  represent H, or R 101  and R 104  together from a bond, and R 102  and R 103  together form a bond.

BACKGROUND OF THE INVENTION

1. Field of the Invention

The present invention relates to compounds capable of suppressing the phosphate concentration of serum, and more particularly to compounds useful for the prevention and treatment of hyperphosphatemia.

2. Related Art

The phosphate concentration of serum is specified by balance between absorption of phosphate from the intestine, intracellular and bone accumulation, filtration into primitive urine in the kidney, and subsequent reabsorption in uriniferous tubules. When the phosphate concentration of serum is not less than 5.0 mg/dl, this condition is called hyperphosphatemia and is a clinical condition that significantly appears mainly in end-stage renal failure and dialysis patients. This is mainly induced by deteriorated excretion of phosphate involved in elimination of renal function. It is also suggested that an increase in phosphate absorption from the intestine derived from the administration of vitamin D participates in this clinical condition. The hyperphosphatemia secondarily leads to hypocalcemia and thus induces secondary hyperparathyroidism which is in turn a principal factor for renal osteodystrophy.

In the prior art technique, to alleviate these clinical conditions, ingestion of a diet having a low phosphate content and the use of a phosphate adsorbent having the function of adsorbing phosphate in the diet have been carried out from the viewpoint of reducing the absorption of phosphate from the intestine. However, it has been pointed out that the diet having a low phosphate content is disadvantageous in that a nutritional disorder is likely to occur, for example, due to lack of ingestion of other nutriments, or observance of this dietary is difficult because the taste is not good. Representative examples of oral phosphate adsorbents include calcium preparations, magnesium preparations, and aluminum preparations. However, it has been pointed out, for example, that the calcium preparations and the magnesium preparations induce hypercalcemia and hypermagnesemia, respectively, and the aluminum preparations induce aluminum osteopathy, aluminum cerebropathy, and dialysis dementia. In recent years, various anion exchange resins have been developed as the oral phosphate adsorbent. Since, however, these anion exchange resins have lower phosphate adsorption capacity than the above group of compounds, a high level of dosage is necessary for phosphate absorption reduction purposes. Therefore, it cannot be said that the compliance for patients is good.

Despite the fact that all the conventional therapeutic agents for hyperphosphatemia suffer from the above problems, up to now, therapeutic agents for hyperphosphatemia which can solve the above problems have not been reported.

Therapeutic agents for hyperphosphatemia are disclosed, for example, in WO 98/03185 and Kidney and Metabolic Bone Diseases, Vol. 15, No. 1 pp 75-80 (2002).

SUMMARY OF THE INVENTION

The present inventors have now found compounds that can inhibit sodium-dependent phosphate transport into rabbit jejunal brush border membrane vesicle (hereinafter referred to as “rabbit BBMV”) and can inhibit sodium-dependent phosphate uptake in Xenopus oocytes, which express sodium-dependent phosphate absorption carrier (NaPi-2a and NaPi-2b), present in the kidney and the small intestine, on cell membranes. The present inventors have also found that compounds having a hydrazine skeleton can lower blood radioactivity of normal rats to which diets containing ³²P, a radioisotope, have been administered orally.

An object of the present invention is to provide compounds and pharmaceutical compositions that can effectively prevent or treat diseases induced by an increase in the phosphate concentration of serum by effectively suppressing the phosphate concentration of serum through a mechanism different from the conventional mechanism.

According to the present invention, there are provided compounds represented by formula (I) and pharmaceutically acceptable salts and solvates thereof:

wherein

A represents a five- to nine-membered unsaturated carbocyclic moiety or a five- to nine-membered unsaturated heterocyclic moiety, and

represents a single bond or a double bond,

the carbocyclic moiety and heterocyclic moiety represented by A are optionally substituted by

(a) a halogen atom;

(b) hydroxyl;

(c) C₁₋₆ alkyl;

(d) C₁₋₆ alkoxy;

(e) aryl;

(f) aryloxy;

(g) arylthio;

(h) alkylthio;

(i) nitro;

(j) amino;

(k) mono- or di-arylamino;

(l) mono- or di-C₁₋₆ alkylamino;

(m) C₂₋₆ alkenyl;

(n) C₂₋₆ alkenyloxy;

(o) C₂₋₆ alkenylthio;

(p) mono- or di-C₂₋₆ alkenylamino;

(q) carboxyl; or

(r) C₁₋₆ alkyl- or aryl-oxycarbonyl;

(c) the C₁₋₆ alkyl group, (d) the C₁₋₆ alkoxy group, (e) the aryl group, (f) the aryloxy group, (g) the arylthio group, (h) the alkylthio group, (m) the C₂₋₆ alkenyl group, (n) the C₂₋₆ alkenyloxy group, and (o) the C₂₋₆ alkenylthio group are optionally substituted by (1) hydroxyl, (2) thiol, (3) amino, (4) C₁₋₆ alkoxy, (5) C₁₋₆ alkylthio, (6) C₁₋₆ alkylsulfonyl, (7) mono- or di-C₁₋₆ alkylamino in which the di-C₁₋₆ alkylamino group may form cyclic amino optionally containing 1 to 3 heteroatoms, (8) aryloxy, (9) arylthio, (10) arylsulfonyl, (11) aryl, (12) a heterocyclic group, (13) a halogen atom, (14) arylamino in which the amino group is optionally substituted by C₁₋₆ alkyl, and the aryl group is optionally substituted by halogen, C₁₋₆ alkyl, C₁₋₆ alkoxy, or C₁₋₆ alkylamino, (15) C₁₋₆ alkoxy-(CH₂CH₂O)m wherein m is an integer of 1 to 6, (16) carboxyl, (17) an oxygen atom (═O), or (18) C₃₋₇ cycloalkyl,

the aryl moiety in (k) the mono- or di-arylamino group is optionally substituted by (1) hydroxyl, (2) thiol, (3) amino, (4) C₁₋₆ alkoxy, (5) C₁₋₆ alkylthio, (6) C₁₋₆ alkylsulfonyl, (7) mono- or di-C₁₋₆ alkylamino in which the di-C₁₋₆ alkylamino group may form cyclic amino optionally containing 1 to 3 heteroatoms, (8) aryloxy, (9) arylthio, (10) arylsulfonyl, (11) aryl, (12) a heterocyclic group, (13) a halogen atom, (14) arylamino in which the amino group is optionally substituted by C₁₋₆ alkyl, and the aryl group is optionally substituted by halogen, C₁₋₆ alkyl, C₁₋₆ alkoxy, or C₁₋₆ alkylamino, (15) C₁₋₆ alkoxy-(CH₂CH₂O)m wherein m is an integer of 1 to 6, (16) carboxyl, (17) an oxygen atom (═O), or (18) C₃₋₇ cycloalkyl, and, in the case of the mono-arylamino group, the amino group is optionally substituted by C₁₋₆ alkyl optionally substituted by hydroxyl or a halogen atom,

in (l) the mono- or di-C₁₋₆ alkylamino, the di-C₁₋₆ alkyl group may form cyclic amino optionally containing 1 to 3 heteroatoms, and one or two alkyl groups on the amino group and the cyclic amino moiety are optionally substituted by a halogen atom; C₁₋₆ alkyl optionally substituted by hydroxyl, a halogen atom, or aryl optionally substituted by a halogen atom, C₁₋₆ alkyl, or C₁₋₆ alkyloxy, a heterocyclic group optionally substituted by a halogen atom, C₁₋₆ alkyl, or C₁₋₆ alkyloxy, and, when one or two alkyl groups on the amino group and the cyclic amino moiety are substituted by two C₁₋₆ alkyl groups, they together may form C₃₋₇ cycloalkyl; C₁₋₆ alkoxy; C₁₋₆ alkylthio; mono- or di-C₁₋₆ alkylamino in which the di-C₁₋₆ alkylamino group may form cyclic amino optionally containing 1 to 3 heteroatoms, and one or two C₁₋₆ alkyl groups on the amino group and the cyclic amino moiety are optionally substituted by hydroxyl or a halogen atom; arylamino in which the amino group is optionally substituted by C₁₋₆ alkyl; mono- or di-C₁₋₆ alkylcarbamoylmethyl in which the di-C₁₋₆ alkylamino group may form cyclic amino optionally containing 1 to 3 heteroatoms, and one or two alkyl groups on the amino group and the cyclic amino moiety are optionally substituted by hydroxyl; aryloxy; arylthio; an oxygen atom; hydroxyl; carboxyl; C₁₋₆ alkoxy- or aryloxy-carbonyl; C₁₋₆ alkylcarbonyl; aryl optionally substituted by a halogen atom or hydroxyl; an oxygen atom (═O); or a heterocyclic group,

in (p) the mono- or di-C₂₋₆ alkenylamino group, the amino group of the monoalkenylamino group is optionally substituted by C₁₋₆ alkyl optionally substituted by hydroxyl or a halogen atom, and the di-C₂₋₆ alkenyl together may form unsaturated cyclic amino optionally containing 1 to 3 heteroatoms, and one or two alkenyl groups on the amino group or the unsaturated cyclic amino moiety are optionally substituted by a halogen atom; C₁₋₆ alkyl optionally substituted by hydroxyl, a halogen atom, aryl optionally substituted by a halogen atom, C₁₋₆ alkyl, or C₁₋₆ alkyloxy, a heterocyclic group optionally substituted by a halogen atom, C₁₋₆ alkyl, or C₁₋₆ alkyloxy, and, when one or two alkyl groups on the amino group and the cyclic amino moiety are substituted by two C₁₋₆ alkyl groups, they together may form C₃₋₇ cycloalkyl; C₁₋₆ alkoxy; C₁₋₆ alkylthio; mono- or di-C₁₋₆ alkylamino in which the di-C₁₋₆ alkylamino group may form cyclic amino optionally containing 1 to 3 heteroatoms, and one or two C₁₋₆ alkyl groups on the amino group and the cyclic amino moiety are optionally substituted by hydroxyl or a halogen atom; arylamino in which the amino group is optionally substituted by C₁₋₆ alkyl; mono- or di-C₁₋₆ alkylcarbamoylmethyl in which the di-C₁₋₆ alkylamino group may form cyclic amino optionally containing 1 to 3 heteroatoms, and one or two alkyl groups on the amino group and the cyclic amino moiety are optionally substituted by hydroxyl; aryloxy; arylthio; an oxygen atom; hydroxyl; carboxyl; C₁₋₆ alkoxy- or aryloxy-carbonyl; C₁₋₆ alkylcarbonyl; aryl optionally substituted by a halogen atom or hydroxyl; an oxygen atom (═O); or a heterocyclic group,

when the carbocyclic moiety and hetrocyclic moiety represented by A are substituted by two (c) C₁₋₆ alkyl groups or (m) C₂₋₆ alkenyl groups, the alkyl or alkenyl groups together with the carbon atoms to which they are respectively attached may form an unsaturated five- to seven-membered carbocyclic ring,

R⁵ represents C₁₋₆ alkyl, aryl, C₁₋₆ alkoxy, aryloxy, C₁₋₆ alkylamino, arylamino, C₁₋₆ alkylthio, arylthio, C₃₋₇ cycloalkyl, or a heterocyclic group, and the C₁₋₆ alkyl, aryl, C₁₋₆ alkoxy, aryloxy, C₁₋₆ alkylamino, arylamino, C₁₋₆ alkylthio, arylthio, C₃₋₇ cycloalkyl, or heterocyclic group represented by R⁵ may be the same or different, and is optionally substituted by

(I) a halogen atom;

(II) C₁₋₆ alkyl optionally containing a substituent selected from the group consisting of (1) hydroxyl, (2) thiol, (3) amino, (4) C₁₋₆ alkoxy, (5) C₁₋₆ alkylthio, (6) C₁₋₆ alkylsulfinyl, (7) C₁₋₆ alkylsulfonyl, (8) mono- or di-C₁₋₆ alkylamino, (8′) amino substituted by a heterocyclic group optionally substituted by C₁₋₆ alkyl, (9) C₁₋₆ alkylcarbonyloxy, (10) C₁₋₆ alkylcarbonylthio, (11) C₁₋₆ alkylcarbonylamino, (12) aryloxy, (13) arylthio, (14) arylsulfinyl, (15) arylsulfonyl, (16) arylamino, (17) C₁₋₆ alkyl- or aryl-sulfonylamino, (18) C₁₋₆ alkyl- or aryl-ureido, (19) C₁₋₆ alkoxy- or aryloxy-carbonylamino, (20) C₁₋₆ alkylamino- or arylamino-carbonyloxy, (21) carboxyl, (22) nitro, (23) a heterocyclic group, (23′) Het-S(═O)j- wherein Het represents a heterocyclic group, j is 0, 1, or 2, and Het is optionally substituted by alkyl optionally substituted by mono- or di-C₁₋₆ alkylamino in which the di-C₁₋₆ alkylamino group may form cyclic amino optionally containing 1 to 3 heteroatoms and one or two alkyl groups on the amino group and the cyclic amino moiety are optionally substituted by hydroxyl, (24) cyano, and (25) a halogen atom,

wherein the alkyl moiety in (4) the C₁₋₆ alkoxy group, (5) the C₁₋₆ alkylthio group, (6) the C₁₋₆ alkylsulfinyl group, and (7) the C₁₋₆ alkylsulfonyl group is optionally substituted by a halogen atom; C₁₋₆ alkyl; C₁₋₆ alkoxy; C₁₋₆ alkylthio; mono- or di-C₁₋₆ alkylamino in which the di-C₁₋₆ alkylamino group may form cyclic amino optionally containing 1 to 3 heteroatoms; aryloxy; arylthio; hydroxyl; carboxyl; —S(═O)₂(—OH); C₁₋₆ alkoxy- or aryloxy-carbonyl; C₁₋₆ alkylcarbonyl; aryl; or a heterocyclic group optionally substituted by alkyl optionally substituted by mono- or di-C₁₋₆ alkylamino in which the di-C₁₋₆ alkylamino group may form cyclic amino optionally containing 1 to 3 heteroatoms, and one or two alkyl groups on the amino group and cyclic amino moiety are optionally substituted by hydroxy, and in (8) the mono- or di-C₁₋₆ alkylamino group, the di-C₁₋₆ alkylamino group may form cyclic amino optionally containing 1 to 3 heteroatoms, and one or two alkyl groups on the amino group and the cyclic amino moiety are optionally substituted by a halogen atom; C₁₋₆ alkyl optionally substituted by hydroxyl, a halogen atom, aryl optionally substituted by a halogen atom, C₁₋₆ alkyl, or C₁₋₆ alkyloxy, or a heterocyclic group optionally substituted by a halogen atom, C₁₋₆ alkyl, or C₁₋₆ alkyloxy, and, when one or two alkyl groups on the amino group and the cyclic amino moiety are substituted by two C₁₋₆ alkyl groups, they together may form C₃₋₇ cycloalkyl; C₁₋₆ alkoxy; C₁₋₆ alkylthio; mono- or di-C₁₋₆ alkylamino in which the di-C₁₋₆ alkylamino may form cyclic amino optionally containing 1 to 3 heteroatoms, and one or two alkyl groups on the amino group and the cyclic amino moiety are optionally substituted by hydroxyl; arylamino in which the amino group is optionally substituted by C₁₋₆ alkyl; mono- or di-C₁₋₆ alkylcarbamoylmethyl in which the di-C₁₋₆ alkylamino group may form cyclic amino optionally containing 1 to 3 heteroatoms, and one or two alkyl groups on the amino group and the cyclic amino moiety are optionally substituted by hydroxyl; aryloxy; arylthio; an oxygen atom (═O); hydroxyl; carboxyl; C₁₋₆ alkoxy- or aryloxy-carbonyl; C₁₋₆ alkylcarbonyl; aryl optionally substituted by a halogen atom or hydroxyl; or a heterocyclic group, preferably a five- to seven-membered saturated or unsaturated heterocyclic ring, more preferably pyridyl, pyrimidyl, or pyridazyl, and, when one carbon atom in the cyclic amino moiety is substituted by two C₁₋₆ alkoxy groups which may be the same or different, the two alkoxy groups together may form group —O—(CH₂)p-O— wherein p is an integer of 2 to 4, and the cyclic amino group may condense with a monocyclic or bicyclic aromatic carbocyclic ring, preferably phenyl or naphthyl, or a monocyclic or bicyclic aromatic heterocyclic ring, preferably pyridyl or naphthyridyl to represent a bicyclic or tricyclic heterocyclic group;

(III) C₁₋₆ alkoxy optionally substituted by a halogen atom;

(IV) C₁₋₆ alkylthio optionally substituted by a halogen atom;

(V) C₃₋₇ cycloalkyl;

(VI) aryl;

(VII) aryloxy;

(VIII) C₁₋₆ alkylcarbonylamino;

(VIX) C₁₋₆ alkylcarbonyloxy;

(X) hydroxyl;

(XI) nitro;

(XII) cyano;

(XIII) amino;

(XIV) mono- or di-C₁₋₆ alkylamino in which the di-C₁₋₆ alkylamino group may form cyclic amino optionally containing 1 to 3 heteroatoms;

(XV) arylamino;

(XVI) C₁₋₆ alkyl- or aryl-sulfonylamino;

(XVII) C₁₋₆ alkyl- or aryl-ureido;

(XVIII) C₁₋₆ alkoxy- or aryloxy-carbonylamino;

(XIX) C₁₋₆ alkylamino- or arylamino-carbonyloxy;

(XX) C₁₋₆ alkoxy- or aryloxy-carbonyl;

(XXI) acyl;

(XXII) carboxyl;

(XXIII) carbamoyl;

(XXIV) mono- or di-alkylcarbamoyl;

(XXV) a heterocyclic group;

(XXVI) alkyl- or aryl-sulfonyl;

(XXVII) C₂₋₆ alkenyloxy group; or

(XXVIII) C₂₋₆ alkynyloxy,

Z represents group (A), group (B), or group (C):

wherein

R⁶ and R⁷, which may be the same or different, represent a hydrogen atom, C₁₋₆ alkyl, C₂₋₆ alkenyl, C₂₋₆ alkynyl, aryl, aryl C₁₋₆ alkyl, aryl C₂₋₆ alkenyl, or a heterocyclic group, and the C₁₋₆ alkyl, aryl, aryl C₁₋₆ alkyl, aryl C₂₋₆ alkenyl, and heterocyclic groups, which may be the same or different, are optionally substituted by:

(I) a halogen atom;

(II) C₁₋₆ alkyl optionally having a substituent selected from a group consisting of (1) hydroxyl, (2) thiol, (3) amino, (4) C₁₋₆ alkoxy, (5) C₁₋₆ alkylthio optionally substituted by hydroxyl, (6) C₁₋₆ alkylsulfinyl, (7) C₁₋₆ alkylsulfonyl, (8) mono- or di-C₁₋₆ alkylamino in which the di-C₁₋₆ alkylamino group may form cyclic amino optionally containing 1 to 3 heteroatoms, (9) C₁₋₆ alkylcarbonyloxy, (10) C₁₋₆ alkylcarbonylthio, (11) C₁₋₆ alkylcarbonylamino, (12) aryloxy, (13) arylthio, (14) arylsulfinyl, (15) arylsulfonyl, (16) arylamino, (17) C₁₋₆ alkyl- or aryl-sulfonylamino, (18) C₁₋₆ alkyl- or aryl-ureido, (19) C₁₋₆ alkoxy- or aryloxy-carbonylamino, (20) C₁₋₆ alkylamino- or arylamino-carbonyloxy, (21) carboxyl, (22) nitro, (23) a heterocyclic group, (23′) Het-S— wherein Het represents a heterocyclic group, (24) cyano, (25) a halogen atom, and (26) C₁₋₆ alkyl- or aryl-oxycarbonyl;

(III) C₁₋₆ alkoxy optionally having a substituent selected from the group consisting of (1) hydroxyl, (2) thiol, (3) amino, (4) C₁₋₆ alkoxy, (5) C₁₋₆ alkylthio optionally substituted by hydroxyl, (6) C₁₋₆ alkylsulfinyl, (7) C₁₋₆ alkylsulfonyl, (8) mono- or di-C₁₋₆ alkylamino in which the di-C₁₋₆ alkylamino group may form cyclic amino optionally containing 1 to 3 heteroatoms, (9) C₁₋₆ alkylcarbonyloxy, (10) C₁₋₆ alkylcarbonylthio, (11) C₁₋₆ alkylcarbonylamino, (12) aryloxy, (13) arylthio, (14) arylsulfinyl, (15) arylsulfonyl, (16) arylamino, (17) C₁₋₆ alkyl- or aryl-sulfonylamino, (18) C₁₋₆ alkyl- or aryl-ureido, (19) C₁₋₆ alkoxy- or aryloxy-carbonylamino, (20) C₁₋₆ alkylamino- or arylamino-carbonyloxy, (21) carboxyl, (22) nitro, (23) a heterocyclic group, (23′) Het-S— wherein Het represents a heterocyclic group, (24) cyano, (25) a halogen atom, and (26) C₁₋₆ alkyl- or aryl-oxycarbonyl;

(IV) C₁₋₆ alkylthio optionally substituted by a halogen atom;

(V) C₃₋₇ cycloalkyl;

(VI) aryl;

(VII) aryloxy;

(VIII) C₁₋₆ alkylcarbonylamino;

(VIX) C₁₋₆ alkylcarbonyloxy;

(X) hydroxyl;

(XI) nitro;

(XII) cyano;

(XIII) amino;

(XIV) mono- or di-C₁₋₆ alkylamino in which the di-C₁₋₆ alkylamino may form cyclic amino optionally containing 1 to 3 heteroatoms;

(XV) arylamino;

(XVI) C₁₋₆ alkyl- or aryl-sulfonylamino;

(XVII) C₁₋₆ alkyl- or aryl-ureido;

(XVIII) C₁₋₆ alkoxy- or aryloxy-carbonylamino;

(XIX) C₁₋₆ alkylamino- or arylamino-carbonyloxy;

(XX) C₁₋₆ alkoxy- or aryloxy-carbonyl;

(XXI) acyl;

(XXII) carboxyl;

(XXIII) carbamoyl;

(XXIV) mono- or di-alkylcarbamoyl;

(XXV) a heterocyclic group;

(XXVI) alkyl- or aryl-sulfonyl;

(XXVII) C₂₋₆ alkenyloxy; or

(XXVIII) C₂₋₆ alkynyloxy,

R¹⁷ represents a hydrogen atom,

R¹⁰¹ and R¹⁰² together represent ═O, and R¹⁰³ and R¹⁰⁴ represent a hydrogen atom, or R¹⁰¹ and R¹⁰⁴ together represent a bond, and R¹⁰² and R¹⁰³ together represent a bond.

Compounds according to the present invention include compounds represented by formula (I-3) and pharmaceutically acceptable salts and solvates thereof:

wherein R²⁰¹, R²⁰², R²⁰³, R²⁰⁴, R^(201′), R^(202′), R^(203′), and R^(204′), which may be the same or different, represent a hydrogen atom, a halogen atom, hydroxyl, C₁₋₆ alkyl, or C₁₋₆ alkoxy,

R²⁰⁵ and R^(205′), which may be the same or different, represent a hydrogen atom or C₁₋₆ alkyl,

R²⁰⁶ and R^(206′), which may be the same or different, represent group A or group B

wherein R⁶ represents a hydrogen atom or C₁₋₆ alkyl, R⁷ represents aryl or a saturated or unsaturated five- or six-membered heterocyclic group in which the aryl group and heterocyclic group are optionally substituted by a halogen atom or C₁₋₆ alkyl optionally substituted by a halogen atom, and

T represents C₂₋₈ alkylene chain.

The pharmaceutical composition according to the present invention comprises the compound according to the present invention.

The pharmaceutical composition according to the present invention may be used for the prevention or treatment of diseases for which serum phosphorus lowering action or phosphate transport inhibition is therapeutically effective. Further, the compounds according to the present invention may be used as a serum phosphorus concentration lowering agent and a phosphate transport inhibitor.

According to the present invention, there is provided use of the compound according to the present invention, for the manufacture of a medicament in the prevention or treatment of diseases for which serum phosphorus lowering action or phosphate transport inhibition is therapeutically effective.

Further, according to the present invention, there is provided use of the compound according to the present invention, for the manufacture of a serum phosphorus concentration lowering agent.

Furthermore, according to the present invention, there is provided use of the compound according to the present invention, for the manufacture of a phosphate transport inhibitor.

Furthermore, according to the present invention, there is provided a method for preventing or treating a disease for which serum phosphorus lowering action or phosphate transport inhibition is therapeutically effective, said method comprising the step of administering a therapeutically or prophylactically effective amount of the compound according to the present invention to a mammal.

Furthermore, according to the present invention, there is provided a method for lowering the concentration of serum phosphorus in a blood stream, said method comprising the step of administering a therapeutically or prophylactically effective amount of the compound according to the present invention to a mammal.

Furthermore, according to the present invention, there is provided a method for inhibiting phosphate transport in vivo, said method comprising the step of administering a therapeutically or prophylactically effective amount of the compound according to the present invention to a mammal.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 shows the inhibition of sodium-dependent phosphate uptake of rabbit jejunal brush border membrane vesicle by compounds according to the present invention;

FIG. 2 shows the inhibition of sodium-dependent glucose uptake of rabbit jejunal brush border membrane vesicle by compounds according to the present invention;

FIG. 3 shows the inhibition of sodium-dependent phosphate uptake of Xenopus oocytes, which have expressed NaPi-2a by compounds according to the present invention; and

FIG. 4 shows the inhibition of sodium-dependent phosphate uptake of Xenopus oocytes, which have expressed NaPi-2a and NaPi-2b by compounds according to the present invention.

DETAILED DESCRIPTION OF THE INVENTION Compounds

The terms “C₁₋₆ alkyl” and “C₁₋₆ alkoxy” as used herein as a group or a part of a group respectively mean straight chain or branched chain alkyl and alkoxy having 1 to 6 carbon atoms. Preferably, the “C₁₋₆ alkyl” and “C₁₋₆ alkoxy” may be C₁₋₄ alkyl and C₁₋₄ alkoxy, respectively.

The term “C₃₋₇ cycloalkyl” as used herein as a group or a part of a group means cyclic alkyl having 3 to 7 carbon atoms. Preferably, the “C₃₋₇ cycloalkyl” is C₅₋₇ cycloalkyl.

The terms “C₂₋₆ alkenyl” and “C₂₋₆ alkynyl” as used herein as a group or a part of a group respectively mean straight chain or branched chain alkenyl having 2 to 6 carbon atoms and alkynyl having 2 to 6 carbon atoms. Preferably, the “C₂₋₆ alkenyl” is C₂₋₄ alkenyl. Preferably, the “C₂₋₆ alkynyl” is C₂₋₄ alkynyl.

Examples of C₁₋₆ alkyl include methyl, ethyl, n-propyl, isopropyl, n-butyl, i-butyl, s-butyl, t-butyl, n-pentyl, and n-hexyl.

Examples of C₁₋₆ alkoxy include methoxy, ethoxy, n-propoxy, i-propoxy, n-butoxy, i-butoxy, s-butoxy, and t-butoxy.

Examples of C₃₋₇ cycloalkyl include cyclopropyl, cyclopentyl, and cyclohexyl.

Examples of C₂₋₆ alkenyl include allyl, butenyl, pentenyl, and hexenyl.

Examples of C₂₋₆ alkynyl include 2-propynyl, butynyl, pentynyl, and hexynyl.

The term “halogen atom” as used herein means a fluorine, chlorine, bromine, or iodine atom.

The terms “unsaturated carbocyclic ring” and “unsaturated heterocyclic ring” as used herein respectively mean carbocyclic ring and heterocyclic ring having one or more unsaturated bonds such as a double bond.

The term “aryl” as used herein means a monocyclic, bicyclic, or tricyclic aromatic hydrocarbon group. Examples of aryl include phenyl, naphthyl, and anthryl.

The term “aryl C₁₋₆ alkyl” as used herein means C₁₋₆ alkyl substituted by a monocyclic, bicyclic, or tricyclic aromatic hydrocarbon group. Examples of aryl C₁₋₆ alkyl include benzyl(C₆H₅CH₂—) and phenethyl(C₆H₅CH₂CH₂—).

The term “arylamino” as used herein means amino substituted by a monocyclic, bicyclic, or tricyclic aromatic hydrocarbon group.

The term “aryl C₂₋₆ alkenyl” as used herein means C₂₋₆ alkenyl substituted by a monocyclic, bicyclic, or tricyclic aromatic hydrocarbon group. Examples of aryl C₂₋₆ alkenyl include phenylethenyl(C₆H₅—CH═CH—).

The term “heterocyclic group” as used herein means a saturated or unsaturated five- to nine-membered (preferably five- to seven-membered, more preferably five- or six-membered) monocyclic heterocyclic group and a saturated or unsaturated nine- to eleven-membered bicyclic heterocyclic group. The heterocyclic group contains one or more heteroatoms selected from oxygen, nitrogen, and sulfur atoms. Examples of the heterocyclic ring include pyridyl, furyl, thienyl, pyrrolyl, pyridazyl, pyrimidyl, pyrazyl, isoxazolyl, quinolyl, quinoxalinyl, and quinazolidyl.

In the di-C₁₋₆ alkylamino group as used herein, two C₁₋₆ alkyl groups attached to the nitrogen atom together may form “cyclic amino.” The term “cyclic amino” as used herein means a saturated five- to eight-membered heterocyclic group formed by combining two C₁₋₆ alkyl groups attached to the nitrogen atom with each other. The cyclic amino group may contain, in addition to the nitrogen atom in the amino group, 1 to 3 heteroatoms, preferably one oxygen atom, one nitrogen atom, or one sulfur atom. Examples of the saturated cyclic amino group include pyrrolidyl, piperidyl, piperazyl, morpholyl, thiomorpholyl, homopiperidyl, and [1,4]diazepine.

In the di-C₂₋₆ alkenylamino group as used herein, two C₂₋₆ alkenyl groups attached to the nitrogen atom together may form “unsaturated cyclic amino.” The term “cyclic amino” as used herein means an unsaturated five- to eight-membered heterocyclic group formed by combining two C₂₋₆ alkenyl groups attached to the nitrogen atom with each other. The cyclic amino group may contain, in addition to the nitrogen atom in the amino group, 1 to 3 heteroatoms, preferably one oxygen atom or one nitrogen atom. Examples of the unsaturated cyclic amino group include pyrrole, pyrazole, imidazolyl, and tetrahydropyridyl.

Compounds represented by formula (I) include hydrazine derivatives and quinazolone derivatives. When R¹⁰¹ and R¹⁰² together represent ═O and R¹⁰³ and R¹⁰⁴ represent a hydrogen atom, formula (I) represents hydrazine derivatives. When R¹⁰¹ and R¹⁰⁴ together represent a bond and when R¹⁰² and R¹⁰³ together represent a bond, formula (I) represent quinazolone derivatives.

In formula (I) and formula (I-1) and formula (I-2) which will be described later, the five- to nine-membered unsaturated carbocyclic moiety or five- to nine-membered unsaturated heterocyclic moiety represented by A may represent, for example, benzene ring moiety, cyclohexene ring moiety, or pyridine ring moiety.

In formula (I) and formula (I-1) and formula (I-2) which will be described later, when the carbocyclic moiety and hetrocyclic moiety represented by A are substituted by two substituents, (c) C₁₋₆ alkyl groups or (m) C₂₋₆ alkenyl groups, these alkyl groups or these alkenyl groups together may form a C₃₋₆ alkylene chain or a C₃₋₆ alkylene chain. In this case, A may represent, for example, naphthyl, quinolyl, benzo[b]thiophene, 4,5,6,7,-tetrahydrobenzo[b]thiophene, cyclopenta[b]thiophene, or quinazolyl.

In formula (I) and formulae (I-1) and (I-2) which will be described later, preferably, the five- to nine-membered unsaturated carbocyclic moiety or the five- to nine-membered unsaturated heterocyclic moiety represented by A may represent formula (IIa) or formula (IIa′):

wherein R¹, R², R³, and R⁴, which may be the same or different, represent

(a) a halogen atom;

(b) hydroxyl;

(c) C₁₋₆ alkyl;

(d) C₁₋₆ alkoxy;

(e) aryl;

(f) aryloxy;

(g) arylthio;

(h) alkylthio;

(i) nitro;

(j) amino;

(i) nitro;

(j) amino;

(k) mono- or di-arylamino;

(l) mono- or di-C₁₋₆ alkylamino;

(m) C₂₋₆ alkenyl;

(n) C₂₋₆ alkenyloxy;

(o) C₂₋₆ alkenylthio;

(p) mono- or di-C₂₋₆ alkenylamino;

(q) carboxyl;

(r) C₁₋₆ alkyl- or aryl-oxycarbonyl; or

(s) a hydrogen atom,

(c) the C₁₋₆ alkyl group, (d) the C₁₋₆ alkoxy group, (e) the aryl group, (f) the aryloxy group, (g) the arylthio group, (h) the alkylthio group, (m) the C₂₋₆ alkenyl group, (n) the C₂₋₆ alkenyloxy group, and (o) the C₂₋₆ alkenylthio group are optionally substituted by (1) hydroxyl, (2) thiol, (3) amino, (4) C₁₋₆ alkoxy, (5) C₁₋₆ alkylthio, (6) C₁₋₆ alkylsulfonyl, (7) mono- or di-C₁₋₆ alkylamino in which the di-C₁₋₆ alkylamino group may form cyclic amino optionally containing 1 to 3 heteroatoms, (8) aryloxy, (9) arylthio, (10) arylsulfonyl, (11) aryl, (12) a heterocyclic group, (13) a halogen atom, or (14) arylamino in which the amino group is optionally substituted by C₁₋₆ alkyl, and the aryl group is optionally substituted by halogen, C₁₋₆ alkyl, C₁₋₆ alkoxy, or C₁₋₆ alkylamino, (15) C₁₋₆ alkoxy-(CH₂CH₂O)m wherein m is an integer of 1 to 6, (16) carboxyl, (17) an oxygen atom (═O), or (18) C₃₋₇ cycloalkyl,

the aryl moiety in (k) the mono- or di-arylamino group is optionally substituted by (1) hydroxyl, (2) thiol, (3) amino, (4) C₁₋₆ alkoxy, (5) C₁₋₆ alkylthio, (6) C₁₋₆ alkylsulfonyl, (7) mono- or di-C₁₋₆ alkylamino in which the di-C₁₋₆ alkylamino group may form cyclic amino optionally containing 1 to 3 heteroatoms, (8) aryloxy, (9) arylthio, (10) arylsulfonyl, (11) aryl, (12) a heterocyclic group, (13) a halogen atom, (14) arylamino in which the amino group is optionally substituted by C₁₋₆ alkyl, and the aryl group is optionally substituted by a halogen atom, C₁₋₆ alkyl, C₁₋₆ alkoxy, or C₁₋₆ alkylamino, (15) C₁₋₆ alkoxy-(CH₂CH₂O)m wherein m is an integer of 1 to 6, (16) carboxyl, (17) an oxygen atom (═O), or (18) C₃₋₇ cycloalkyl, and, in the case of the mono-arylamino group, the amino group is optionally substituted by C₁₋₆ alkyl optionally substituted by hydroxyl or a halogen atom,

in (l) the mono- or di-C₁₋₆ alkylamino, the di-C₁₋₆ alkyl group may form cyclic amino optionally containing 1 to 3 heteroatoms, and one or two alkyl groups on the amino group and the cyclic amino moiety are optionally substituted by a halogen atom; C₁₋₆ alkyl optionally substituted by hydroxyl, a halogen atom, or aryl optionally substituted by a halogen atom, C₁₋₆ alkyl, or C₁₋₆ alkyloxy, a heterocyclic group optionally substituted by a halogen atom, C₁₋₆ alkyl, or C₁₋₆ alkyloxy, and, when one or two alkyl groups on the amino group and the cyclic amino moiety are substituted by two C₁₋₆ alkyl groups, they together may form C₃₋₇ cycloalkyl; C₁₋₆ alkoxy; C₁₋₆ alkylthio; mono- or di-C₁₋₆ alkylamino in which the di-C₁₋₆ alkylamino group may form cyclic amino optionally containing 1 to 3 heteroatoms, and one or two C₁₋₆ alkyl groups on the amino group and the cyclic amino moiety are optionally substituted by hydroxyl or a halogen atom; arylamino in which the amino group is optionally substituted by C₁₋₆ alkyl; mono- or di-C₁₋₆ alkylcarbamoylmethyl in which the di-C₁₋₆ alkylamino group may form cyclic amino optionally containing 1 to 3 heteroatoms, and one or two alkyl groups on the amino group and the cyclic amino moiety are optionally substituted by hydroxyl; aryloxy; arylthio; an oxygen atom (═O); hydroxyl; carboxyl; C₁₋₆ alkoxy- or aryloxy-carbonyl; C₁₋₆ alkylcarbonyl; aryl optionally substituted by a halogen atom or hydroxyl; or a heterocyclic group,

in (p) the mono- or di-C₂₋₆ alkenylamino group, the amino group of the monoalkenylamino group is optionally substituted by C₁₋₆ alkyl optionally substituted by hydroxyl or a halogen atom, and the di-C₂₋₆ alkenyl together may form unsaturated cyclic amino optionally containing 1 to 3 heteroatoms, and one or two alkenyl groups on the amino group or the unsaturated cyclic amino moiety is optionally substituted by a halogen atom; C₁₋₆ alkyl optionally substituted by hydroxyl, a halogen atom, aryl optionally substituted by a halogen atom, C₁₋₆ alkyl, or C₁₋₆ alkyloxy, a heterocyclic group optionally substituted by a halogen atom, C₁₋₆ alkyl, or C₁₋₆ alkyloxy, and, when one or two alkyl groups on the amino group and the cyclic amino moiety are substituted by two C₁₋₆ alkyl groups, they together may form C₃₋₇ cycloalkyl; C₁₋₆ alkoxy; C₁₋₆ alkylthio; mono- or di-C₁₋₆ alkylamino in which the di-C₁₋₆ alkylamino group may form cyclic amino optionally containing 1 to 3 heteroatoms, and one or two C₁₋₆ alkyl groups on the amino group and the cyclic amino moiety are optionally substituted by hydroxyl or a halogen atom; arylamino in which the amino group is optionally substituted by C₁₋₆ alkyl; mono- or di-C₁₋₆ alkylcarbamoylmethyl in which the di-C₁₋₆ alkylamino group may form cyclic amino optionally containing 1 to 3 heteroatoms, and one or two alkyl groups on the amino group and the cyclic amino moiety are optionally substituted by hydroxyl; aryloxy; arylthio; an oxygen atom (═O); hydroxyl; carboxyl; C₁₋₆ alkoxy- or aryloxy-carbonyl; C₁₋₆ alkylcarbonyl; aryl optionally substituted by a halogen atom or hydroxyl; or a heterocyclic group,

when the carbocyclic moiety and hetrocyclic moiety represented by A are substituted by two (c) C₁₋₆ alkyl groups or (m) C₂₋₆ alkenyl groups, preferably when positions of R² and R³ are substituted, the alkyl or alkenyl groups together with the carbon atoms to which they are respectively attached may form an unsaturated five- to seven-membered carbocyclic ring, and

* represents a bond to —C(═O)—N(—Z)(—R¹⁰⁴).

In formula (I) and formula (I-1) and formula (I-2) which will be described later, A may represent formula (IIa), and, in this case, preferably R¹, R², R³, and R⁴ represent

(a) a halogen atom;

(b) hydroxyl;

(c) C₁₋₆ alkyl;

(d) C₁₋₆ alkoxy;

(e) aryl;

(f) aryloxy;

(g) arylthio;

(h) alkylthio;

(i) nitro;

(j) amino; or

(k) a hydrogen atom, and

(c) the C₁₋₆ alkyl group, (d) the C₁₋₆ alkoxy group, (e) the aryl group, (f) the aryloxy group, (g) the arylthio group, and (h) the alkylthio group are optionally substituted by (1) hydroxyl, (2) thiol, (3) amino, (4) C₁₋₆ alkoxy, (5) C₁₋₆ alkylthio, (6) C₁₋₆ alkylsulfonyl, (7) mono- or di-C₁₋₆ alkylamino in which the di-C₁₋₆ alkylamino group may form cyclic amino optionally containing 1 to 3 heteroatoms, (8) aryloxy, (9) arylthio, (10) arylsulfonyl, (11) aryl, (12) a heterocyclic group, (13) a halogen atom, or (14) arylamino in which the amino group is optionally substituted by C₁₋₆ alkyl, and the aryl group is optionally substituted by halogen, C₁₋₆ alkyl, C₁₋₆ alkoxy, or C₁₋₆ alkylamino.

In formula (I) and formula (I-1) and formula (I-2) which will be described later, when A represents formula (IIa) or formula (IIa′), preferably, R¹, R³, and R⁴, which may be the same or different, represent

a hydrogen atom;

a halogen atom;

C₁₋₆ alkyl in which the alkyl group is optionally substituted by C₁₋₆ alkoxy or a halogen atom;

aryl optionally substituted by C₁₋₆ alkoxy or a halogen atom;

C₁₋₆ alkoxy in which the alkoxy group is optionally substituted by C₁₋₆ alkoxy or a halogen atom; or

aryloxy optionally substituted by C₁₋₆ alkoxy or a halogen atom,

R² may represent

a hydrogen atom;

a halogen atom;

hydroxyl;

C₁₋₆ alkyl in which the alkyl group is optionally substituted by (1) hydroxyl, (2) thiol, (3) amino, (4) C₁₋₆ alkoxy, (5) C₁₋₆ alkylthio, (6) C₁₋₆ alkylsulfonyl, (7) mono- or di-C₁₋₆ alkylamino in which the di-C₁₋₆ alkylamino group may form cyclic amino optionally containing 1 to 3 heteroatoms, (8) aryloxy, (9) arylthio, (10) arylsulfonyl, (11) aryl, (12) a heterocyclic group, (13) a halogen atom, or (14) arylamino in which the amino group is optionally substituted by C₁₋₆ alkyl, and the aryl group is optionally substituted by a halogen atom, C₁₋₆ alkyl, C₁₋₆ alkoxy, or C₁₋₆ alkylamino; or

C₁₋₆ alkoxy in which the alkoxy group is optionally substituted by (1) hydroxyl, (2) thiol, (3) amino, (4) C₁₋₆ alkoxy, (5) C₁₋₆ alkylthio, (6) C₁₋₆ alkylsulfonyl, (7) mono- or di-C₁₋₆ alkylamino in which di-C₁₋₆ alkylamino may form cyclic amino optionally containing 1 to 3 heteroatoms, (8) aryloxy, (9) arylthio, (10) arylsulfonyl, (11) aryl, (12) a heterocyclic group, or (13) a halogen atom,

more preferably,

R¹, R³, and R⁴ represent a hydrogen atom,

R² represents

a halogen atom;

hydroxyl;

C₁₋₆ alkyl optionally substituted by mono- or di-C₁₋₆ alkylamino; or

C₁₋₆ alkoxy optionally substituted by mono- or di-C₁₋₆ alkylamino.

In formula (I) and formula (I-1) and formula (I-2) which will be described later, when A represents formula (IIa) or formula (IIa′), preferably, R¹, R², R³, and R⁴, which may be the same or different, represent a hydrogen atom; a halogen atom; hydroxyl; optionally substituted C₁₋₆ alkyl; optionally substituted C₂₋₆ alkenyl; optionally substituted C₁₋₆ alkoxy; optionally substituted mono- or di-arylamino; optionally substituted mono- or di-C₁₋₆ alkylamino in which the dialkylamino together may form optionally substituted cyclic amino optionally containing 1 to 3 heteroatoms; optionally substituted mono- or di-C₂₋₆ alkenylamino in which the di-C₂₋₆ alkenylamino group together may form optionally substituted unsaturated cyclic amino optionally containing 1 to 3 heteroatoms, and, when R² and R³ are optionally substituted C₁₋₆ alkyl or optionally substituted C₂₋₆ alkenyl, the alkyl or alkenyl groups together with the carbon atoms to which R² and R³ are respectively attached may form an unsaturated five- to seven-membered carbocyclic ring, and, more preferably, R¹ and R⁴ represent a hydrogen atom.

In formula (I) and formula (I-1) and formula (I-2) which will be described later, when A represents formula (IIa) or formula (IIa′), preferably, R¹, R², R³, and R⁴, which may be the same or different, represent a hydrogen atom; a halogen atom; hydroxyl; optionally substituted C₁₋₆ alkyl; or optionally substituted C₁₋₆ alkoxy, and more preferably, R¹ and R⁴ represent a hydrogen atom.

In formula (I) and formula (I-1) and formula (I-2) which will be described later, when A represents formula (IIa) or formula (IIa′), R¹, R², R³, and R⁴ more preferably represent a hydrogen atom.

In formula (I) and formula (I-1) and formula (I-2) which will be described later, when A represents formula (IIa) or formula (IIa′), more preferably,

R¹ and R⁴ represent a hydrogen atom,

any one of R² and R³, preferably R², represents a halogen atom; hydroxyl; C₁₋₆ alkyl optionally having a substituent, preferably a halogen atom, mono- or di-alkylamino which may form cyclic amino, or hydroxyl; C₁₋₆ alkoxy optionally having a substituent, preferably a halogen atom, mono- or di-alkylamino which may form cyclic amino, hydroxyl, C₁₋₆ alkoxy-(CH₂CH₂O)m, wherein m is an integer of 1 to 6, or C₃₋₇ cycloalkyl; optionally substituted mono- or di-arylamino; mono- or di-C₁₋₆ alkylamino optionally having a substituent, preferably hydroxyl, C₁₋₆ alkyl optionally substituted by hydroxyl, an oxygen atom (═O), mono- or di-C₁₋₆ alkylamino which may form cyclic amino, or carboxyl, and the dialkylamino together may form cyclic amino optionally having a substituent, preferably hydroxyl, C₁₋₆ alkyl optionally substituted by hydroxyl, an oxygen atom (═O), mono- or di-C₁₋₆ alkylamino which may form cyclic amino, or carboxyl, and the cyclic amino group may contain 1 to 3 heteroatoms; optionally substituted mono- or di-C₂₋₆ alkenylamino, in which the di-C₂₋₆ alkenylamino group together may form optionally substituted unsaturated cyclic amino optionally containing 1 to 3 heteroatoms, and the other (preferably, R³) represents a hydrogen atom.

In the above preferred embodiment, more preferably, the cyclic amino group may be a five- to seven-membered heterocyclic group that optionally contains one oxygen atom, one nitrogen atom, or one sulfur atom in addition to the nitrogen atom in the amino group. Particularly preferred saturated cyclic amino groups include pyrrolidyl, piperidyl, piperazyl, morpholyl, thiomorpholyl, homopiperidyl, and [1,4]diazepine.

In formula (I) and formula (I-1) and formula (I-2) which will be described later, when A represents formula (IIa) or formula (IIa′), more preferably, R¹ and R⁴ represent a hydrogen atom, and any one of R² and R³ represents a halogen atom; hydroxyl; optionally substituted C₁₋₆ alkyl; optionally substituted C₁₋₆ alkoxy with the other representing a hydrogen atom.

In formula (I) and formula (I-1) and formula (I-2) which will be described later, when A represents formula (IIa) or formula (IIa′), more preferably, R¹ and R⁴ represent a hydrogen atom, and R² and R³, which may be the same or different, represent a halogen atom; hydroxyl; C₁₋₆ alkyl optionally having a substituent, preferably a halogen atom, mono- or di-alkylamino group which may form cyclic amino, or hydroxyl; C₁₋₆ alkoxy optionally having a substituent, preferably a halogen atom, mono- or di-alkylamino which may form cyclic amino, hydroxyl, C₁₋₆ alkoxy-(CH₂CH₂O)m wherein m is an integer of 1 to 6, or C₃₋₇ cycloalkyl.

In the above preferred embodiment, more preferably, the cyclic amino group may be a five- to seven-membered heterocyclic group that optionally contains one oxygen atom, one nitrogen atom, or one sulfur atom in addition to the nitrogen atom in the amino group. Particularly preferred saturated cyclic amino groups include pyrrolidyl, piperidyl, piperazyl, morpholyl, thiomorpholyl, homopiperidyl, and [1,4]diazepine.

In formula (I) and formula (I-1) and formula (I-2) which will be described later, when A represents formula (IIa) or formula (IIa′), more preferably, R¹ and R⁴ represent a hydrogen atom, and R² and R³ together with the carbon atoms to which they are respectively attached form an unsaturated five- to seven-membered carbocyclic ring. Particularly preferably, group A together with R² and R³ forms naphthyl or quinolyl.

In formula (I) and formula (I-1) and formula (I-2) which will be described later, when A represents formula (IIa) or formula (IIa′), more preferably, R¹ and R⁴ represent a hydrogen atom, and R² and R³, which may be the same or different, represent C₁₋₆ alkoxy optionally having a substituent (C₁₋₆ alkoxy-(CH₂CH₂O) m wherein m is an integer of 1 to 6).

In formula (I) and formula (I-1) and formula (I-2) which will be described later, when A represents formula (IIa) or formula (IIa′), more preferably, R¹ and R⁴ represent a hydrogen atom; any one of R² and R³ (preferably, R²) represents mono- or di-C₁₋₆ alkylamino optionally having a substituent, preferably hydroxyl, C₁₋₆ alkyl optionally substituted by hydroxyl, an oxygen atom (═O), mono- or di-C₁₋₆ alkylamino which may form cyclic amino, or carboxyl, and the dialkylamino group together may form cyclic amino optionally having a substituent, preferably hydroxyl, C₁₋₆ alkyl optionally substituted by hydroxyl, an oxygen atom (═O), mono- or di-C₁₋₆ alkylamino which may form cyclic amino, or carboxyl, and the cyclic amino group may contain 1 to 3 heteroatoms; and the other (preferably, R³) represents a hydrogen atom.

In the above preferred embodiment, more preferably, the cyclic amino group may be a five- to seven-membered heterocyclic group that optionally contains one oxygen atom, one nitrogen atom, or one sulfur atom in addition to the nitrogen atom in the amino group. Particularly preferred saturated cyclic amino groups include pyrrolidyl, piperidyl, piperazyl, morpholyl, thiomorpholyl, homopiperidyl, and [1,4]diazepine.

In formula (I) and formula (I-1) and formula (I-2) which will be described later, when A represents formula (IIa) or formula (IIa′), more preferably, R¹ and R⁴ represent a hydrogen atom; any one of R² and R³ (preferably, R²) represents C₁₋₆ alkoxy optionally having a substituent, preferably a halogen atom, mono- or di-alkylamino which may form cyclic amino, hydroxyl, C₁₋₆ alkoxy-(CH₂CH₂O)m wherein m is an integer of 1 to 6, or C₃₋₇ cycloalkyl; and the other (preferably, R³) represents a hydrogen atom.

In the above preferred embodiment, more preferably, the cyclic amino group may be a five- to seven-membered heterocyclic group that optionally contains one oxygen atom, one nitrogen atom, or one sulfur atom in addition to the nitrogen atom in the amino group. Particularly preferred saturated cyclic amino groups include pyrrolidyl, piperidyl, piperazyl, morpholyl, thiomorpholyl, homopiperidyl, and [1,4]diazepine.

In formula (I) and formula (I-1) and formula (I-2) which will be described later, preferably, the five- to nine-membered unsaturated carbocyclic moiety or the five- to nine-membered unsaturated heterocyclic moiety represented by A represents formula (IIb):

wherein R³¹ and R³², which may be the same or different, represent a hydrogen atom; a halogen atom; or C₁₋₆ alkyl in which the alkyl group is optionally substituted by (1) hydroxyl, (2) thiol, (3) amino, (4) C₁₋₆ alkoxy, (5) C₁₋₆ alkylthio, (6) C₁₋₆ alkylsulfonyl, (7) mono- or di-C₁₋₆ alkylamino in which the di-C₁₋₆ alkylamino may form cyclic amino optionally containing 1 to 3 heteroatoms, (8) aryloxy, (9) arylthio, (10) arylsulfonyl, (11) aryl, (12) a heterocyclic group, (13) a halogen atom, or (14) arylamino in which the amino group is optionally substituted by C₁₋₆ alkyl, and the aryl group is optionally substituted by a halogen, C₁₋₆ alkyl, C₁₋₆ alkoxy, or C₁₋₆ alkylamino; or C₂₋₆ alkenyl,

when R³¹ and R³² represent alkyl or alkenyl, the alkyl or alkenyl groups together with the carbon atoms to which they are respectively attached may form an unsaturated five- to seven-membered carbocyclic ring, and

* represents a bond to —C(═O)—N(—Z)(—R¹⁰⁴).

In formula (I) and formula (I-1) and formula (I-2) which will be described later, when A represents formula (IIb), preferably,

R³¹ and R³², which may be the same or different, represent a hydrogen atom; a halogen atom; or C₁₋₆ alkyl in which the alkyl group is optionally substituted by (1) hydroxyl, (2) thiol, (3) amino, (4) C₁₋₆ alkoxy, (5) C₁₋₆ alkylthio, (6) C₁₋₆ alkylsulfonyl, (7) mono- or di-C₁₋₆ alkylamino in which the di-C₁₋₆ alkylamino may form cyclic amino optionally containing 1 to 3 heteroatoms, (8) aryloxy, (9) arylthio, (10) arylsulfonyl, (11) aryl, (12) a heterocyclic group, (13) a halogen atom, or (14) arylamino in which the amino group is optionally substituted by C₁₋₆ alkyl, and the aryl group is optionally substituted by a halogen, C₁₋₆ alkyl, C₁₋₆ alkoxy, or C₁₋₆ alkylamino,

when R³¹ and R³² represent alkyl, the alkyl groups together with the carbon atoms to which they are respectively attached may form an unsaturated five- to seven-membered carbocyclic ring, and, in this case, R³¹ and R³² together form a C₃₋₅ alkylene chain, and

represents a double bond.

In formula (I) and formula (I-1) and formula (I-2) which will be described later, when A represents formula (IIb), more preferably,

(i) R³¹ and R³² represent a hydrogen atom, or (ii) any one of R³¹ and R³² represents a hydrogen atom, and the other represents C₁₋₆ alkyl optionally substituted by mono- or di-C₁₋₆ alkylamino, which may form cyclic amino, preferably piperidyl, morpholyl, and thiomorpholyl, or by a halogen atom, and the cyclic amino group may contain 1 to 3 heteroatoms, or (iii) R³¹ and R³², which may be the same or different, represent C₁₋₆ alkyl optionally substituted by mono- or di-C₁₋₆ alkylamino, which may form cyclic amino, preferably piperidyl, morpholyl, and thiomorpholyl, or by a halogen atom, and the cyclic amino group may contain 1 to 3 heteroatoms, or (iv) R³¹ and R³² together with the carbon atoms to which they are respectively attached form a saturated or unsaturated five- to seven-membered carbocyclic ring, preferably a cyclohexane ring, a benzene ring, and a cyclopentane ring.

In formula (I) and formula (I-1) and formula (I-2) which will be described later, when A represents formula (IIb), more preferably, R³¹ and R³² represent a hydrogen atom, or any one of R³¹ and R³² represents a hydrogen atom with the other representing C₁₋₆ alkyl optionally substituted by a halogen atom, or R³¹ and R³² together with the carbon atoms to which they are respectively attached form an unsaturated five- to seven-membered carbocyclic ring. In this case, R³¹ and R³² together may form a C₃₋₆ alkylene chain, and

may represent a double bond.

In formula (I) and formula (I-1) and formula (I-2) which will be described later, preferably, the five- to nine-membered unsaturated carbocyclic moiety or the five- to nine-membered unsaturated heterocyclic moiety represented by A represents formula (IIc):

wherein R³³ and R³⁴, which may be the same or different, represent a hydrogen atom; a halogen atom; or C₁₋₆ alkyl in which the alkyl group is optionally substituted by (1) hydroxyl, (2) thiol, (3) amino, (4) C₁₋₆ alkoxy, (5) C₁₋₆ alkylthio, (6) C₁₋₆ alkylsulfonyl, (7) mono- or di-C₁₋₆ alkylamino in which the di-C₁₋₆ alkylamino may form cyclic amino optionally containing 1 to 3 heteroatoms, (8) aryloxy, (9) arylthio, (10) arylsulfonyl, (11) aryl, (12) a heterocyclic group, (13) a halogen atom, or (14) arylamino in which the amino group is optionally substituted by C₁₋₆ alkyl, and the aryl group is optionally substituted by a halogen, C₁₋₆ alkyl, C₁₋₆ alkoxy, or C₁₋₆ alkylamino,

when R³³ and R³⁴ represent alkyl, the alkyl groups together with the carbon atoms to which they are respectively attached may form an unsaturated five- to seven-membered carbocyclic ring, and

* represents a bond to —C(═O)—N(—Z)(—R¹⁰⁴).

In formula (I) and formula (I-1) and formula (I-2) which will be described later, when A represents formula (IIc), preferably,

R³³ and R³⁴, which may be the same or different, represent a hydrogen atom; a halogen atom; or C₁₋₆ alkyl in which the alkyl group is optionally substituted by (1) hydroxyl, (2) thiol, (3) amino, (4) C₁₋₆ alkoxy, (5) C₁₋₆ alkylthio, (6) C₁₋₆ alkylsulfonyl, (7) mono- or di-C₁₋₆ alkylamino in which the di-C₁₋₆ alkylamino may form cyclic amino optionally containing 1 to 3 heteroatoms, (8) aryloxy, (9) arylthio, (10) arylsulfonyl, (11) aryl, (12) a heterocyclic group, (13) a halogen atom, or (14) arylamino in which the amino group is optionally substituted by C₁₋₆ alkyl, and the aryl group is optionally substituted by a halogen, C₁₋₆ alkyl, C₁₋₆ alkoxy, or C₁₋₆ alkylamino,

when R³³ and R³⁴ represent alkyl, the alkyl groups together with the carbon atoms to which they are respectively attached may form an unsaturated five- to seven-membered carbocyclic ring, and, in this case, R³³ and R³⁴ together form a C₃₋₅ alkylene chain, and

represents a double bond.

In formula (I) and formula (I-1) and formula (I-2) which will be described later, when A represents formula (IIc), more preferably,

(i) R³³ and R³⁴ represent a hydrogen atom, or (ii) any one of R³³ and R³⁴ represents a hydrogen atom, and the other represents C₁₋₆ alkyl optionally substituted by mono- or di-C₁₋₆ alkylamino, which may form cyclic amino, preferably piperidyl, morpholyl, and thiomorpholyl, or by a halogen atom, and the cyclic amino group may contain 1 to 3 heteroatoms, or (iii) R³³ and R³⁴, which may be the same or different, represent C₁₋₆ alkyl optionally substituted by mono- or di-C₁₋₆ alkylamino, which may form cyclic amino, preferably piperidyl, morpholyl, and thiomorpholyl, or by a halogen atom, and the cyclic amino group may contain 1 to 3 heteroatoms, or (iv) R³³ and R³⁴ together with the carbon atoms to which they are respectively attached form a saturated or unsaturated five- to seven-membered carbocyclic ring, preferably a cyclohexane ring, a benzene ring, and a cyclopentane ring.

In formula (I) and formula (I-1) and formula (I-2) which will be described later, when A represents formula (IIc), more preferably, R³³ and R³⁴ represent a hydrogen atom, or any one of R³³ and R³⁴ represents a hydrogen atom with the other representing C₁₋₆ alkyl optionally substituted by a halogen atom, or R³³ and R³⁴ together with the carbon atoms to which they are respectively attached form an unsaturated five- to seven-membered carbocyclic ring. In this case, R³³ and R³⁴ together may form a C₃₋₅ alkylene chain, and

may represent a double bond.

In formula (I) and formula (I-1) and formula (I-2) which will be described later, preferably, the five- to nine-membered saturated or unsaturated carbocyclic moiety or the five- to nine-membered saturated or unsaturated heterocyclic moiety represented by A represents formula (IId):

wherein R³⁵ and R³⁶, which may be the same or different, represent a hydrogen atom; a halogen atom; or C₁₋₆ alkyl in which the alkyl group is optionally substituted by (1) hydroxyl, (2) thiol, (3) amino, (4) C₁₋₆ alkoxy, (5) C₁₋₆ alkylthio, (6) C₁₋₆ alkylsulfonyl, (7) mono- or di-C₁₋₆ alkylamino in which the di-C₁₋₆ alkylamino may form cyclic amino optionally containing 1 to 3 heteroatoms, (8) aryloxy, (9) arylthio, (10) arylsulfonyl, (11) aryl, (12) a heterocyclic group, (13) a halogen atom, or (14) arylamino in which the amino group is optionally substituted by C₁₋₆ alkyl, and the aryl group is optionally substituted by a halogen, C₁₋₆ alkyl, C₁₋₆ alkoxy, or C₁₋₆ alkylamino; or C₂₋₆ alkenyl, and

* represents a bond to —C(═O)—N(—Z)(—R¹⁰⁴).

In formula (I) and formula (I-1) and formula (I-2) which will be described later, when A represents formula (IId), more preferably, R³⁵ and R³⁶ represent a hydrogen atom, or any one of R³⁵ and R³⁶ represents a hydrogen atom with the other representing C₁₋₆ alkyl optionally substituted by a halogen atom.

In formula (I) and formula (I-1) and formula (I-2) which will be described later, preferably, R⁵ may represent optionally substituted C₆₋₇ cycloalkyl, optionally substituted aryl, more preferably phenyl or naphthyl, an optionally substituted saturated or unsaturated five- or six-membered heterocyclic group, more preferably pyridyl, furyl, thienyl, isoxazole, and pyrimidyl, or an optionally substituted saturated or unsaturated nine- to eleven-membered bicyclic heterocyclic group, more preferably quinoxalinyl.

In formula (I) and formula (I-1) and formula (I-2) which will be described later, particularly preferably, R⁵ represents a cyclic group selected from C₅₋₇ cycloalkyl, phenyl, pyridyl, furyl, thienyl, isoxazole, pyrimidyl, and quinoxalinyl, in which the cyclic group is optionally substituted by a halogen atom; C₁₋₆ alkyl optionally substituted by a halogen atom; C₁₋₆ alkoxy optionally substituted by a halogen atom; or hydroxyl.

In formula (I) and formula (I-1) and formula (I-2) which will be described later, particularly preferably, R⁵ represents a cyclic group selected from C₅₋₇ cycloalkyl, phenyl, pyridyl, furyl, thienyl, isoxazole, pyrimidyl, and quinoxalinyl, in which the cyclic group is optionally substituted by C₁₋₆ alkyl in which the alkyl group is optionally substituted by optionally substituted C₁₋₆ alkoxy, optionally substituted C₁₋₆ alkylthio, optionally substituted C₁₋₆ alkylsulfinyl, optionally substituted C₁₋₆ alkylsulfonyl, or optionally substituted mono- or di-C₁₋₆ alkylamino in which the di-C₁₋₆ alkylamino may form cyclic amino optionally containing 1 to 3 heteroatoms.

In formula (I) and formula (I-1) and formula (I-2) which will be described later, preferably, R⁵ represents a group of formula (IIIa), (IIIb), or (IIIc):

wherein

D, E, J, L, and M, which may be the same or different, represent a carbon or nitrogen atom,

G represents an oxygen or sulfur atom,

R⁸, R⁹, R¹⁰, R¹¹, and R¹², which may be the same or different, represent

(I) a halogen atom;

(II) C₁₋₆ alkyl optionally containing a substituent selected from the group consisting of (1) hydroxyl, (2) thiol, (3) amino, (4) C₁₋₆ alkoxy, (5) C₁₋₆ alkylthio, (6) C₁₋₆ alkylsulfinyl, (7) C₁₋₆ alkylsulfonyl, (8) mono- or di-C₁₋₆ alkylamino, (8′) amino substituted by a heterocyclic group optionally substituted by C₁₋₆ alkyl, (9) C₁₋₆ alkylcarbonyloxy, (10) C₁₋₆ alkylcarbonylthio, (11) C₁₋₆ alkylcarbonylamino, (12) aryloxy, (13) arylthio, (14) arylsulfinyl, (15) arylsulfonyl, (16) arylamino, (17) C₁₋₆ alkyl- or aryl-sulfonylamino, (18) C₁₋₆ alkyl- or aryl-ureido, (19) C₁₋₆ alkoxy- or aryloxy-carbonylamino, (20) C₁₋₆ alkylamino- or arylamino-carbonyloxy, (21) carboxyl, (22) nitro, (23) a heterocyclic group, (23′) Het-S(═O)j- wherein Het represents a heterocyclic group, j is 0, 1, or 2, and Het is optionally substituted by alkyl optionally substituted by mono- or di-C₁₋₆ alkylamino in which the di-C₁₋₆ alkylamino group may form cyclic amino optionally containing 1 to 3 heteroatoms and one or two alkyl groups on the amino group and the cyclic amino moiety are optionally substituted by hydroxyl, (24) cyano, and (25) a halogen atom,

wherein the alkyl moiety in (4) the C₁₋₆ alkoxy group, (5) the C₁₋₆ alkylthio group, (6) the C₁₋₆ alkylsulfinyl group, and (7) the C₁₋₆ alkylsulfonyl group is optionally substituted by a hydrogen atom, a halogen atom; C₁₋₆ alkyl; C₁₋₆ alkoxy; C₁₋₆ alkylthio; mono- or di-C₁₋₆ alkylamino in which the di-C₁₋₆ alkylamino group may form cyclic amino optionally containing 1 to 3 heteroatoms; aryloxy; arylthio; hydroxyl; carboxyl; —S(═O)₂(—OH); C₁₋₆ alkoxy- or aryloxy-carbonyl; C₁₋₆ alkylcarbonyl; aryl; or a heterocyclic group optionally substituted by alkyl optionally substituted by mono- or di-C₁₋₆ alkylamino in which the di-C₁₋₆ alkylamino group may form cyclic amino optionally containing 1 to 3 heteroatoms, and one or two alkyl groups on the amino group and the cyclic amino moiety are optionally substituted by hydroxy, and in (8) the mono- or di-C₁₋₆ alkylamino group, the di-C₁₋₆ alkylamino group may form cyclic amino optionally containing 1 to 3 heteroatoms, and one or two alkyl groups on the amino group and the cyclic amino moiety are optionally substituted by a halogen atom; C₁₋₆ alkyl optionally substituted by hydroxyl, a halogen atom, aryl optionally substituted by a halogen atom, C₁₋₆ alkyl, or C₁₋₆ alkyloxy, or a heterocyclic group optionally substituted by a halogen atom, C₁₋₆ alkyl, or C₁₋₆ alkyloxy, and, when one or two alkyl groups on the amino group and the cyclic amino moiety are substituted by two C₁₋₆ alkyl groups, they together may form C₃₋₇ cycloalkyl; C₁₋₆ alkoxy; C₁₋₆ alkylthio; mono- or di-C₁₋₆ alkylamino in which the di-C₁₋₆ alkylamino may form cyclic amino optionally containing 1 to 3 heteroatoms, and one or two alkyl groups on the amino group and the cyclic amino moiety are optionally substituted by hydroxyl; arylamino in which the amino group is optionally substituted by C₁₋₆ alkyl; mono- or di-C₁₋₆ alkylcarbamoylmethyl in which the di-C₁₋₆ alkylamino group may form cyclic amino optionally containing 1 to 3 heteroatoms, and one or two alkyl groups on the amino group and the cyclic amino moiety are optionally substituted by hydroxyl; aryloxy; arylthio; an oxygen atom (═O); hydroxyl; carboxyl; C₁₋₆ alkoxy- or aryloxy-carbonyl; C₁₋₆ alkylcarbonyl; aryl optionally substituted by a halogen atom or hydroxyl; or a heterocyclic group, preferably a five- to seven-membered saturated or unsaturated heterocyclic group, more preferably pyridyl, pyrimidyl, and pyridazyl, and, when one carbon atom in the cyclic amino moiety is substituted by two C₁₋₆ alkoxy groups which may be the same or different, the two alkoxy groups together may form group —O—(CH₂)p—O— wherein p is an integer of 2 to 4, and the cyclic amino group may condense with a monocyclic or bicyclic aromatic carbocyclic ring, preferably phenyl or naphthyl, or a monocyclic or bicyclic aromatic heterocyclic ring, preferably pyridyl or naphthyridyl, to represent a bicyclic or tricyclic heterocyclic group;

(III) C₁₋₆ alkoxy optionally substituted by a halogen atom;

(IV) C₁₋₆ alkylthio optionally substituted by a halogen atom;

(V) C₃₋₇ cycloalkyl;

(VI) aryl;

(VII) aryloxy;

(VIII) C₁₋₆ alkylcarbonylamino;

(VIX) C₁₋₆ alkylcarbonyloxy;

(X) hydroxyl;

(XI) nitro;

(XII) cyano;

(XIII) amino;

(XIV) mono- or di-C₁₋₆ alkylamino in which the di-C₁₋₆ alkylamino group may form cyclic amino optionally containing 1 to 3 heteroatoms;

(XV) arylamino;

(XVI) C₁₋₆ alkyl- or aryl-sulfonylamino;

(XVII) C₁₋₆ alkyl- or aryl-ureido;

(XVIII) C₁₋₆ alkoxy- or aryloxy-carbonylamino;

(XIX) C₁₋₆ alkylamino- or arylamino-carbonyloxy;

(XX) C₁₋₆ alkoxy- or aryloxy-carbonyl;

(XXI) acyl;

(XXII) carboxyl;

(XXIII) carbamoyl;

(XXIV) mono- or di-alkylcarbamoyl;

(XXV) a heterocyclic group;

(XXVI) alkyl- or aryl-sulfonyl;

(XXVII) C₂₋₆ alkenyloxy;

(XXVIII) C₂₋₆ alkynyloxy; or

(XXIX) a hydrogen atom, and

when D, E, J, L, or M represents a nitrogen atom, R⁸, R⁹, R¹⁰, R¹¹, and R¹² each are absent, or otherwise together with a nitrogen atom may form N-oxide (N→O).

In formula (I) and formula (I-1) and formula (I-2) which will be described later, when R⁵ represents formula (IIIa), formula (IIIb) and formula (IIIc), preferably, R⁸, R⁹, R¹⁰, R¹¹, and R¹², which may be the same or different, represent

a hydrogen atom;

a halogen atom;

hydroxymethyl; or

C₁₋₆ alkyl optionally substituted by a halogen atom.

In formula (I) and formula (I-1) and formula (I-2) which will be described later, when R⁵ represents formula (IIIa), formula (IIIb) and formula (IIIc), preferably, the substituted C₁₋₆ alkyl which may be represented by R⁸, R⁹, R¹⁰, R¹¹, and R¹² represents a group of formula (IV):

—CH₂-Q—X1-R¹³  (Iv)

wherein

Q represents an oxygen atom, a sulfur atom, sulfinyl, or sulfonyl,

X1 represents a bond or straight chain or branched chain alkylene having 1 to 5 carbon atoms,

R¹³ represents a hydrogen atom, a halogen atom, C₁₋₆ alkyl, C₁₋₆ alkoxy, C₁₋₆ alkylthio, mono- or di-C₁₋₆ alkylamino in which the di-C₁₋₆ alkylamino group may form cyclic amino optionally containing 1 to 3 heteroatoms, aryloxy, arylthio, hydroxyl, carboxyl, —S(═O)₂(—OH), C₁₋₆ alkoxy- or aryloxy-carbonyl, C₁₋₆ alkylcarbonyl, aryl, or a heterocyclic group optionally substituted by C₁₋₆ alkyl optionally substituted by mono- or di-C₁₋₆ alkylamino in which the di-C₁₋₆ alkylamino group may form cyclic amino optionally containing 1 to 3 heteroatoms, and one or two alkyl groups on the amino group and the cyclic amino moiety are optionally substituted by hydroxyl, and this heterocyclic group preferably represents a five- or six-membered saturated or unsaturated heterocyclic group;

or a group of formula (V)

wherein

X2 represents a bond or straight chain or branched chain alkylene having 1 to 5 carbon atoms,

X3 represents a bond or straight chain or branched chain alkylene having 1 to 5 carbon atoms,

R¹⁴ and R¹⁵, which may be the same or different, represent a hydrogen atom; a halogen atom; C₁₋₆ alkyl optionally substituted by hydroxyl, a halogen atom, aryl optionally substituted by a halogen atom, C₁₋₆ alkyl, or C₁₋₆ alkyloxy, a heterocyclic group optionally substituted by a halogen atom, C₁₋₆ alkyl, or C₁₋₆ alkyloxy, and, when one or two alkyl groups on the amino group and the cyclic amino moiety are substituted by two C₁₋₆ alkyl groups, they together may form C₃₋₇ cycloalkyl; C₁₋₆ alkoxy; C₁₋₆ alkylthio; mono- or di-C₁₋₆ alkylamino in which the di-C₁₋₆ alkylamino group may form cyclic amino optionally containing 1 to 3 heteroatoms, and one or two alkyl groups on the amino group and the cyclic amino moiety are optionally substituted by hydroxyl; arylamino in which the amino group is optionally substituted by C₁₋₆ alkyl; mono- or di-C₁₋₆ alkylcarbamoylmethyl in which the di-C₁₋₆ alkylamino may form cyclic amino optionally containing 1 to 3 heteroatoms, and one or two alkyl groups on the amino group and the cyclic amino moiety are optionally substituted by hydroxyl; aryloxy; arylthio; an oxygen atom (═O); hydroxyl; carboxyl; C₁₋₆ alkoxy- or aryloxy-carbonyl; C₁₋₆ alkylcarbonyl; aryl optionally substituted by a halogen atom or hydroxyl; or a heterocyclic group, preferably a five- or six-membered saturated or unsaturated heterocyclic group, provided that, when X2 represents a bond, R¹⁴ represents a hydrogen atom, or when X3 represents a bond, R¹⁵ represents a hydrogen atom, or

R¹⁴ and R¹⁵ together with a nitrogen atom to which they are respectively attached may form a heterocyclic group that may contain 1 to 3 heteroatoms, preferably one oxygen atom, one nitrogen atom, or one sulfur atom, in addition to the nitrogen atom, to which R¹⁴ and R¹⁵ are attached, and is optionally substituted by hydroxyl; C₁₋₆ alkyl optionally substituted by hydroxyl, a halogen atom, aryl optionally substituted by a halogen atom, C₁₋₆ alkyl, or C₁₋₆ alkyloxy, or a heterocyclic group optionally substituted by a halogen atom, C₁₋₆ alkyl, or C₁₋₆ alkyloxy, and, when one or two alkyl groups on the amino group and the cyclic amino moiety are substituted by two C₁₋₆ alkyl groups, they together may form C₃₋₇ cycloalkyl; mono- or di-C₁₋₆ alkylamino in which the di-C₁₋₆ alkylamino may form cyclic amino optionally containing 1 to 3 heteroatoms, and one or two alkyl groups on the amino group and the cyclic amino moiety are optionally substituted by hydroxyl; a saturated or unsaturated five- or six-membered heterocyclic group; mono- or di-C₁₋₆ alkylcarbamoylmethyl in which the di-C₁₋₆ alkylamino group may form cyclic amino optionally containing 1 to 3 heteroatoms, and one or two alkyl groups on the amino group and the cyclic amino moiety are optionally substituted by hydroxyl; phenyl; or an oxygen atom (═O), and, when one carbon atom in the cyclic amino moiety is substituted by two C₁₋₆ alkoxy groups which may be the same or different, the two alkoxy groups together may form group —O—(CH₂)p-O— wherein p is an integer of 2 to 4, and the cyclic amino group may condense with a monocyclic or bicyclic aromatic carbocyclic ring, preferably phenyl or naphthyl, or a monocyclic or bicyclic aromatic heterocyclic ring, preferably pyridyl or naphthyridyl, to represent a bicyclic or tricyclic heterocyclic group.

Preferably, the cyclic amino group present in formula (IV) and formula (V) may be a five- to seven-membered heterocyclic group that optionally contains one oxygen atom, one nitrogen atom, or one sulfur atom in addition to the nitrogen atom in the amino group, more preferably piperidyl, piperazyl, morpholyl, and thiomorpholyl.

In formula (I) and formula (I-1) and formula (I-2) which will be described later, when R⁵ represents formula (IIIa), formula (IIIb) or formula (IIIc), preferably, D, E, J, L, and M represent a carbon atom.

In formula (I) and formula (I-1) and formula (I-2) which will be described later, when R⁵ represents formula (IIIa), formula (IIIb) or formula (IIIc), preferably, any one or two of D, E, J, L, and M represent a nitrogen atom and the others represent a carbon atom.

In formula (I) and formula (I-1) and formula (I-2) which will be described later, when R⁵ represents formula (IIIa), preferably, D, E, J, L, and M represent a carbon atom.

In formula (I) and formula (I-1) and formula (I-2) which will be described later, when R⁵ represents formula (IIIa), preferably, any one or two of D, E, J, L, and M represent a nitrogen atom with the others representing a carbon atom.

In formula (I) and formula (I-1) and formula (I-2) which will be described later, when R⁵ represents formula (IIIb), preferably, D, E, and J represent a carbon atom, and G represents an oxygen or sulfur atom.

In formula (I) and formula (I-1) and formula (I-2) which will be described later, when R⁵ represents formula (IIIc), preferably, D, E, and J represent a carbon atom, and G represents an oxygen or sulfur atom.

In formula (I) and formula (I-1) and formula (I-2) which will be described later, when R⁵ represents formula (IIIa), preferably, D, E, J, L, and M represent a carbon atom, any one of R⁸, R⁹, R¹⁰, R¹¹, and R¹² represents a group other than a hydrogen atom, and the others represent a hydrogen atom.

In formula (I) and formula (I-1) and formula (I-2) which will be described later, when R⁵ represents formula (IIIa), preferably, D, E, J, L, and M represent a carbon atom, any one of R⁸, R⁹, R¹⁰, R¹¹, and R¹² represents a halogen atom; optionally substituted C₁₋₆ alkyl; or optionally substituted C₁₋₆ alkoxy, and the other groups represent a hydrogen atom.

In formula (I) and formula (I-1) and formula (I-2) which will be described later, when R⁵ represents formula (IIIa), preferably, D, E, J, L, and M represent a carbon atom, R¹⁰ represents a group other than a hydrogen atom, preferably substituted C₁₋₆ alkyl, more preferably a group of formula (IV) or formula (V), and R⁸, R⁹, R¹¹, and R¹² represent a hydrogen atom.

In formula (I) and formula (I-1) and formula (I-2) which will be described later, when R⁵ represents formula (IIIa), preferably, D, E, J, L, and M represent a carbon atom, R¹¹ represents a group other than a hydrogen atom, preferably substituted C₁₋₆ alkyl, more preferably a group of formula (IV) or formula (V), and R⁸, R⁹, R¹⁰, and R¹² represent a hydrogen atom.

In formula (I) and formula (I-1) and formula (I-2) which will be described later, when R⁵ represents formula (IIIa), preferably, D, E, J, L, and M represent a carbon atom, and any two of R⁸, R⁹, R¹⁰, R¹¹, and R¹² represent a group other than a hydrogen atom with the others representing a hydrogen atom.

In formula (I) and formula (I-1) and formula (I-2) which will be described later, when R⁵ represents formula (IIIa), preferably, D, E, J, L, and M represent a carbon atom, R¹⁰ and R¹¹ represent a group other than a hydrogen atom, preferably optionally substituted C₁₋₆ alkoxy, more preferably optionally substituted methoxy, and R⁸, R⁹, and R¹² represent a hydrogen atom.

In formula (I) and formula (I-1) and formula (I-2) which will be described later, when R⁵ represents formula (IIIa), preferably, D, E, J, L, and M represent a carbon atom, R⁹ and R¹¹ represent a group other than a hydrogen atom, preferably, optionally substituted C₁₋₆ alkoxy, more preferably optionally substituted methoxy, and R⁸, R¹⁰, and R¹² represent a hydrogen atom.

In formula (I) and formula (I-1) and formula (I-2) which will be described later, when R⁵ represents formula (IIIb) and formula (IIIc), preferably, D, E, and J represent a carbon atom.

In formula (I) and formula (I-1) and formula (I-2) which will be described later, when R⁵ represents formula (IIIb) and formula (IIIc), preferably, any one or two of D, E, and J represent a nitrogen atom with the other(s) representing a carbon atom.

In formula (I) and formula (I-1) and formula (I-2) which will be described later, when R⁵ represents formula (IIIa), preferably,

D, E, J, L, and M represent a carbon atom,

any one or two of R⁸, R⁹, R¹⁰, R¹¹, and R¹², which may be the same or different, represent a halogen atom; hydroxymethyl; C₁₋₆ alkyl optionally substituted by a halogen atom; or C₁₋₆ alkoxy optionally substituted by a halogen atom, and the others represent a hydrogen atom.

In formula (I) and formula (I-1) and formula (I-2) which will be described later, when R⁵ represents formula (IIIa), preferably, any one or two of D, E, J, L, and M represent a nitrogen atom, and the others represent a carbon atom, any one or two of R⁸, R⁹, R¹⁰, R¹¹, and R¹², which may be the same or different, represent a halogen atom; hydroxymethyl; C₁₋₆ alkyl optionally substituted by a halogen atom, or C₁₋₆ alkoxy optionally substituted by a halogen atom, and the others represent a hydrogen atom.

In formula (I) and formula (I-1) and formula (I-2) which will be described later, when R⁵ represents formula (IIIb), preferably,

D, E, and J represent a carbon atom, and G represents an oxygen or sulfur atom,

one or two of R⁸, R⁹, and R¹⁰, which may be the same or different, represent a halogen atom; hydroxymethyl; C₁₋₆ alkyl optionally substituted by a halogen atom; or C₁₋₆ alkoxy optionally substituted by a halogen atom, and the others represent a hydrogen atom.

In formula (I) and formula (I-1) and formula (I-2) which will be described later, when R⁵ represents formula (IIIc), preferably,

D, E, and J represent a carbon atom, and G represents an oxygen or sulfur atom,

one or two of R⁸, R⁹, and R¹⁰, which may be the same or different, represent a halogen atom; hydroxymethyl; C₁₋₆ alkyl optionally substituted by a halogen atom; or C₁₋₆ alkoxy optionally substituted by a halogen atom, and the others represent a hydrogen atom.

In formula (I) and formula (I-1) and formula (I-2) which will be described later, when R⁵ represents formula (IIIa), preferably,

D, E, J, L, and M represent a carbon atom,

R⁸, R⁹, and R¹² represent a hydrogen atom,

one of R¹⁰ and R¹¹ represents a group of formula (IV) wherein Q, X1, and R¹³ are as defined above, or a group of formula (V) wherein X2, X3, R¹⁴, and R¹⁵ are as defined above with the other groups representing a hydrogen atom.

In formula (I) and formula (I-1) and formula (I-2) which will be described later, when R⁵ represents formula (IIIa), preferably,

any one or two of D, E, J, L, and M represent a nitrogen atom, and the others represent a carbon atom,

R⁸, R⁹, and R¹² represent a hydrogen atom,

one of R¹⁰ and R¹¹ represents a group of formula (IV) wherein Q, X1, and R¹³ are as defined above, or a group of formula (V) wherein X2, X3, R¹⁴, and R¹⁵ are as defined above with the other groups representing a hydrogen atom.

In formula (I) and formula (I-1) and formula (I-2) which will be described later, when R⁵ represents formula (IIIb), preferably,

D, E, and J represent a carbon atom, and G represents an oxygen or sulfur atom,

one of R⁸, R⁹, and R¹⁰ represents a group of formula (IV) wherein Q, X1, and R¹³ are as defined above, or a group of formula (V) wherein X2, X3, R¹⁴, and R¹⁵ are as defined above with the others representing a hydrogen atom.

In formula (I) and formula (I-1) and formula (I-2) which will be described later, when R⁵ represents formula (IIIc), preferably,

D, E, and J represent a carbon atom, and G represents an oxygen or sulfur atom,

one of R⁸, R⁹, and R¹⁰ represents a group of formula (IV) wherein Q, X1, and R¹³ are as defined above, or a group of formula (V) wherein X2, X3, R¹⁴, and R¹⁵ are as defined above with the others representing a hydrogen atom.

In formula (I) and formula (I-1) and formula (I-2) which will be described later, preferably, R⁶ represents a hydrogen atom; optionally substituted C₁₋₆ alkyl; or optionally substituted aryl.

In formula (I) and formula (I-1) and formula (I-2) which will be described later, more preferably, R⁶ represents a hydrogen atom; C₁₋₆ alkyl optionally substituted by a halogen atom or C₁₋₆ alkoxy; or aryl optionally substituted by a halogen atom, C₁₋₆ alkyl, or C₁₋₆ alkoxy, most preferably, a hydrogen atom, or C₁₋₆ alkyl.

In formula (I) and formula (I-1) and formula (I-2) which will be described later, preferably, R⁷ represents optionally substituted aryl, optionally substituted aryl C₁₋₆ alkyl, optionally substituted aryl C₂₋₆ alkenyl, or optionally substituted saturated or unsaturated five- or six-membered heterocyclic group.

In formula (I) and formula (I-1) and formula (I-2) which will be described later, more preferably, R⁷ represents a cyclic group selected from phenyl, naphthyl, furyl, pyrrolyl, and thienyl, and the cyclic group is optionally substituted by a halogen atom; C₁₋₆ alkyl optionally substituted by a halogen atom; C₁₋₆ alkoxy in which the alkoxy group is optionally substituted by a halogen atom, aryloxy optionally substituted by a halogen atom and C₁₋₆ alkyl, C₁₋₆ alkoxy in which the alkoxy group is optionally substituted by mono- or di-C₁₋₆ alkylamine in which the di-C₁₋₆ alkylamino group may form cyclic amino optionally containing 1 to 3 heteroatoms, or a halogen atom, arylthio optionally substituted by a halogen atom and C₁₋₆ alkyl, C₁₋₆ alkylthio in which the alkylthio group is optionally substituted by mono- or di-C₁₋₆ alkylamine in which the di-C₁₋₆ alkylamino group may form cyclic amino optionally containing 1 to 3 heteroatoms, or a halogen atom, arylamino optionally substituted by C₁₋₆ alkyl, mono- or di-C₁₋₆ alkylamine in which the di-C₁₋₆ alkylamino group may form cyclic amino optionally containing 1 to 3 heteroatoms; hydroxyl; mono- or di-C₁₋₆ alkylamino in which the di-C₁₋₆ alkylamino group may form cyclic amino optionally containing 1 to 3 heteroatoms; nitro; C₂₋₆ alkenyloxy; or C₂₋₆ alkynyloxy.

In formula (I) and formula (I-1) and formula (I-2) which will be described later, preferably, R⁶ represents a hydrogen atom or C₁₋₆ alkyl, R⁷ represents optionally substituted aryl, preferably phenyl or naphthyl, optionally substituted aryl, preferably phenyl or naphthyl, C₁₋₆ alkyl, optionally substituted aryl, preferably phenyl or naphthyl, C₂₋₆ alkenyl, or optionally substituted saturated or unsaturated five- or six-membered heterocyclic group, preferably furyl, thienyl, pyrrolyl, or pyridyl.

Among the compounds of formula (I), hydrazine derivatives may be represented by formula (I-1).

wherein A, R⁵, Z, and

are as defined in formula (I).

In formula (I-1), preferably,

A represents formula (IIa) or formula (IIa′) wherein R¹, R², R³, and R⁴ are as defined in formula (IIa) and formula (IIa′) and are preferably the same or different and represent a hydrogen atom; a halogen atom; hydroxyl; optionally substituted C₁₋₆ alkyl; or optionally substituted C₁₋₆ alkoxy,

R⁵ represents optionally substituted C₅₋₇ cycloalkyl, optionally substituted aryl, preferably phenyl, or optionally substituted saturated or unsaturated five- or six-membered heterocyclic group, preferably pyridyl, thienyl, isoxazole, or pyrimidyl and more preferably represents a group of formula (IIIa), formula (IIIb) or formula (IIIc), and

Z represents group (A), group (B), or group (C) wherein R⁶ represents a hydrogen atom or C₁₋₆ alkyl, R⁷ represents optionally substituted aryl, preferably phenyl or naphthyl, optionally substituted aryl, preferably phenyl or naphthyl, C₁₋₆ alkyl, optionally substituted aryl, preferably phenyl or naphthyl, C₂₋₆ alkenyl, or optionally substituted saturated or unsaturated five- or six-membered heterocyclic group, preferably furyl, thienyl, pyrrolyl, or pyridyl, and R¹⁷ represents a hydrogen atom.

In formula (I-1), preferably,

A represents formula (IIa) wherein R¹, R², R³, and R⁴ are as defined in formula (IIa),

represents a double bond,

R⁵ represents optionally substituted C₅₋₇ cycloalkyl, optionally substituted aryl, or optionally substituted saturated or unsaturated five- or six-membered heterocyclic group, preferably pyridyl, thienyl, isoxazole, or pyrimidyl and more preferably represents a group of formula (IIIa), formula (IIIb), or formula (IIIc), and

Z represents group (A) or group (B) wherein R⁶ represents a hydrogen atom or C₁₋₆ alkyl, R⁷ represents optionally substituted aryl, preferably phenyl, optionally substituted aryl C₁₋₆ alkyl, optionally substituted aryl C₂₋₆ alkenyl, or optionally substituted saturated or unsaturated five- or six-membered heterocyclic group, and R¹⁷ represents a hydrogen atom.

In formula (I-1), preferably,

A represents formula (IIb) wherein R³¹ and R³² are as defined in formula (IIb), preferably, R³¹ and R³² represent a hydrogen atom, or any one of R³¹ and R³² represents a hydrogen atom with the other representing C₁₋₆ alkyl optionally substituted by a halogen atom, or R³¹ and R³² together form a C₃₋₅ alkylene chain,

R⁵ represents optionally substituted C₅₋₇ cycloalkyl, optionally substituted aryl, preferably phenyl, or optionally substituted saturated or unsaturated five- or six-membered heterocyclic group, preferably pyridyl, thienyl, isoxazole, or pyrimidyl, more preferably represents a group of formula (IIIa), formula (IIIb), or formula (IIIc), and

Z represents group (A) or group (B) wherein R⁶ represents a hydrogen atom or C₁₋₆ alkyl, R⁷ represents optionally substituted aryl, optionally substituted aryl C₁₋₆ alkyl, optionally substituted aryl C₂₋₆ alkenyl, or optionally substituted saturated or unsaturated five- or six-membered heterocyclic group, and R¹⁷ represents a hydrogen atom.

In formula (I-1), preferably,

A represents formula (IIc) wherein R³³ and R³⁴ are as defined in formula (IIc), and, preferably, R³³ and R³⁴ represent a hydrogen atom, or any one of R³³ and R³⁴ represents a hydrogen atom with the other representing C₁₋₆ alkyl optionally substituted by a halogen atom, or R³³ and R³⁴ together form a C₃₋₅ alkylene chain,

R⁵ represents optionally substituted C₅₋₇ cycloalkyl, optionally substituted aryl, preferably phenyl, or optionally substituted saturated or unsaturated five- or six-membered heterocyclic group, preferably pyridyl, thienyl, isoxazole, or pyrimidyl, and more preferably, represents a group of formula (IIIa), formula (IIIb), or formula (IIIc), and

Z represents group (A) and group (B) wherein R⁶ represents a hydrogen atom or C₁₋₆ alkyl, R⁷ represents optionally substituted aryl, optionally substituted aryl C₁₋₆ alkyl, optionally substituted aryl C₂₋₆ alkenyl, or optionally substituted saturated or unsaturated five- or six-membered heterocyclic group, and R¹⁷ represents a hydrogen atom.

In formula (I-1), preferably,

A represents formula (IId) wherein R³⁵ and R³⁶ are as defined in formula (IId), and, preferably, R³⁵ and R³⁶ represent a hydrogen atom, or any one of R³⁵ and R³⁶ represents a hydrogen atom with the other representing C₁₋₆ alkyl optionally substituted by a halogen atom,

R⁵ represents optionally substituted C₆₋₇ cycloalkyl, optionally substituted aryl, preferably phenyl, or optionally substituted saturated or unsaturated five- or six-membered heterocyclic group, preferably pyridyl, thienyl, isoxazole, or pyrimidyl, and more preferably represents a group of formula (IIIa), formula (IIIb), or formula (IIIc),

Z represents group (A) or group (B) wherein R⁶ represents a hydrogen atom or C₁₋₆ alkyl, R⁷ represents optionally substituted aryl, optionally substituted aryl C₁₋₆ alkyl, optionally substituted aryl C₂₋₆ alkenyl, or optionally substituted saturated or unsaturated five- or six-membered heterocyclic group, and R¹⁷ represents a hydrogen atom.

In formula (I-1), more preferably,

A represents formula (IIa) or formula (IIa′),

wherein

(1) R¹, R², R³, and R⁴ represent a hydrogen atom, (2) R¹ and R⁴ represent a hydrogen atom, any one of R² and R³ represents a halogen atom; hydroxyl; optionally substituted C₁₋₆ alkyl; optionally substituted C₁₋₆ alkoxy; optionally substituted mono- or di-arylamino; optionally substituted mono- or di-C₁₋₆ alkylamino in which the dialkylamino together may form optionally substituted cyclic amino optionally containing 1 to 3 heteroatoms; or optionally substituted mono- or di-C₂₋₆ alkenylamino in which the di-C₂₋₆ alkenylamino group together may form optionally substituted unsaturated cyclic amino optionally containing 1 to 3 heteroatoms, and the other represents a hydrogen atom, (3) R¹ and R⁴ represent a hydrogen atom, and R² and R³, which may be the same or different, represent a halogen atom; hydroxyl; optionally substituted C₁₋₆ alkyl; or optionally substituted C₁₋₆ alkoxy, (4) R¹ and R⁴ represent a hydrogen atom, and R² and R³ together with the carbon atoms to which they are respectively attached form a saturated or unsaturated five- to seven-membered carbocyclic ring, (5) R¹ and R⁴ represent a hydrogen atom, any one of R² and R³ represents optionally substituted mono- or di-C₁₋₆ alkylamino in which the di-C₁₋₆ alkylamino together may form optionally substituted cyclic amino optionally containing 1 to 3 heteroatoms, and the other represents a hydrogen atom, or (6) R¹ and R⁴ represent a hydrogen atom, any one of R² and R³ represents optionally substituted C₁₋₆ alkoxy, and the other represents a hydrogen atom,

R⁵ represents formula (IIIa)

wherein

(i) D, E, J, L, and M represent a carbon atom, any one or two of R⁸, R⁹, R¹⁰, R¹¹, and R¹², which may be the same or different, represent a halogen atom; hydroxymethyl; C₁₋₆ alkyl optionally substituted by a halogen atom; or C₁₋₆ alkoxy optionally substituted by a halogen atom, and the others represent a hydrogen atom, (ii) any one or two of D, E, J, L, and M represent a nitrogen atom, and the others represent a carbon atom, any one or two of R⁸, R⁹, R¹⁰, R¹¹, and R¹² may be the same or different and represent a halogen atom; hydroxymethyl; C₁₋₆ alkyl optionally substituted by a halogen atom, or C₁₋₆ alkoxy optionally substituted by a halogen atom, and the others represent a hydrogen atom, (iii) D, E, J, L, and M represent a carbon atom, R⁸, R⁹, and R¹² represent a hydrogen atom, any one of R¹⁰ and R¹¹ represents a group of formula (IV) wherein Q, X1, and R¹³ are as defined above, or a group of formula (V) wherein X2, X3, R¹⁴, and R¹⁵ are as defined above, and the other represents a hydrogen atom, or (iv) any one or two of D, E, J, L, and M represent a nitrogen atom, and the others represent a carbon atom, R⁸, R⁹, and R¹² represent a hydrogen atom, and one of R¹⁰ and R¹¹ represents a group of formula (IV) wherein Q, X1, and R¹³ are as defined above, or a group of formula (V) wherein X2, X3, R¹⁴, and R¹⁵ are as defined above, and the other represents a hydrogen atom,

Z represents group (A), group (B), or group (C):

wherein

R⁶ represents a hydrogen atom or C₁₋₆ alkyl,

R⁷ represents optionally substituted aryl, optionally substituted aryl C₁₋₆ alkyl, optionally substituted aryl C₂₋₆ alkenyl, or optionally substituted saturated or unsaturated five- or six-membered heterocyclic group, and

R¹⁷ represents a hydrogen atom.

In formula (I-1), more preferably,

A represents formula (IIa) or formula (IIa′)

wherein

(1) R¹, R², R³, and R⁴ represent a hydrogen atom, (2) R¹ and R⁴ represent a hydrogen atom, any one of R² and R³ represents a halogen atom; hydroxyl; optionally substituted C₁₋₆ alkyl; optionally substituted C₁₋₆ alkoxy; optionally substituted mono- or di-arylamino; optionally substituted mono- or di-C₁₋₆ alkylamino in which the dialkylamino together may form optionally substituted cyclic amino optionally containing 1 to 3 heteroatoms; or optionally substituted mono- or di-C₂₋₆ alkenylamino in which the di-C₂₋₆ alkenylamino group together may form optionally substituted unsaturated cyclic amino optionally containing 1 to 3 heteroatoms, and the other represents a hydrogen atom, (3) R¹ and R⁴ represent a hydrogen atom, and R² and R³, which may be the same or different, represent a halogen atom; hydroxyl; optionally substituted C₁₋₆ alkyl; or optionally substituted C₁₋₆ alkoxy, (4) R¹ and R⁴ represent a hydrogen atom, and R² and R³ together with the carbon atoms to which they are respectively attached form a saturated or unsaturated five- to seven-membered carbocyclic ring, (5) R¹ and R⁴ represent a hydrogen atom, any one of R² and R³ represents optionally substituted mono- or di-C₁₋₆ alkylamino in which the di-C₁₋₆ alkylamino together may form optionally substituted cyclic amino optionally containing 1 to 3 heteroatoms, and the other represents a hydrogen atom, or (6) R¹ and R⁴ represent a hydrogen atom, any one of R² and R³ represents optionally substituted C₁₋₆ alkoxy, and the other represents a hydrogen atom,

R⁵ represents formula (IIIb) or formula (IIIc)

wherein

(i) D, E, and J represent a carbon atom, G represents an oxygen or sulfur atom, any one or two of R⁸, R⁹, and R¹⁰, which may be the same or different, represent a halogen atom; hydroxymethyl; C₁₋₆ alkyl optionally substituted by a halogen atom; or C₁₋₆ alkoxy optionally substituted by a halogen atom, and the others represent a hydrogen atom, or (ii) D, E, and J represent a carbon atom, G represents an oxygen or sulfur atom, one of R⁸, R⁹, and R¹⁰ represents a group of formula (IV) wherein Q, X1, and R¹³ are as defined above, or a group of formula (V) wherein X2, X3, R¹⁴, and R¹⁵ are as defined above, and the others represent a hydrogen atom,

Z represents group (A), group (B), or group (C):

wherein

R⁶ represents a hydrogen atom or C₁₋₆ alkyl,

R⁷ represents optionally substituted aryl, optionally substituted aryl C₁₋₆ alkyl, optionally substituted aryl C₂₋₆ alkenyl, or optionally substituted saturated or unsaturated five- or six-membered heterocyclic group, and

R¹⁷ represents a hydrogen atom.

In formula (I-1), more preferably,

A represents formula (IIb)

wherein

(i) R³¹ and R³² represent a hydrogen atom, (ii) any one of R³¹ and R³² represents a hydrogen atom, and the other represents C₁₋₆ alkyl optionally substituted by mono- or di-C₁₋₆ alkylamino, which may form cyclic amino, or a halogen atom, and the cyclic amino group may contain 1 to 3 heteroatoms, (iii) R³¹ and R³², which may be the same or different, represent C₁₋₆ alkyl optionally substituted by mono- or di-C₁₋₆ alkylamino, which may form cyclic amino, or a halogen atom, and the cyclic amino group may contain 1 to 3 heteroatoms, or (iv) R³¹ and R³² together with the carbon atoms to which they are respectively attached form a saturated or unsaturated five- to seven-membered carbocyclic ring,

R⁵ represents formula (IIIa)

wherein

(i) D, E, J, L, and M represent a carbon atom, any one or two of R⁸, R⁹, R¹⁰, R¹¹, and R¹², which may be the same or different, represent a halogen atom; hydroxymethyl; C₁₋₆ alkyl optionally substituted by a halogen atom; or C₁₋₆ alkoxy optionally substituted by a halogen atom, and the others represent a hydrogen atom, (ii) any one or two of D, E, J, L, and M represent a nitrogen atom, and the others represent a carbon atom, any one or two of R⁸, R⁹, R¹⁰, R¹¹, and R¹² may be the same or different and represent a halogen atom; hydroxymethyl; C₁₋₆ alkyl optionally substituted by a halogen atom, or C₁₋₆ alkoxy optionally substituted by a halogen atom, and the others represent a hydrogen atom, (iii) D, E, J, L, and M represent a carbon atom, R⁸, R⁹, and R¹² represent a hydrogen atom, any one of R¹⁰ and R¹¹ represents a group of formula (IV) wherein Q, X1, and R¹³ are as defined above, or a group of formula (V) wherein X2, X3, R¹⁴, and R¹⁵ are as defined above, and the other represents a hydrogen atom, or (iv) any one or two of D, E, J, L, and M represent a nitrogen atom, and the others represent a carbon atom, R⁸, R⁹, and R¹² represent a hydrogen atom, and one of R¹⁰ and R¹¹ represents a group of formula (IV) wherein Q, X1, and R¹³ are as defined above, or a group of formula (V) wherein X2, X3, R¹⁴, and R¹⁵ are as defined above, and the other represents a hydrogen atom,

Z represents group (A), group (B), or group (C):

wherein

R⁶ represents a hydrogen atom or C₁₋₆ alkyl,

R⁷ represents optionally substituted aryl, optionally substituted aryl C₁₋₆ alkyl, optionally substituted aryl C₂₋₆ alkenyl, or optionally substituted saturated or unsaturated five- or six-membered heterocyclic group, and

R¹⁷ represents a hydrogen atom.

In formula (I-1), more preferably,

A represents formula (IIb)

wherein

(i) R³¹ and R³² represent a hydrogen atom, (ii) any one of R³¹ and R³² represents a hydrogen atom, and the other represents C₁₋₆ alkyl optionally substituted by mono- or di-C₁₋₆ alkylamino, which may form cyclic amino, or a halogen atom, and the cyclic amino group may contain 1 to 3 heteroatoms, (iii) R³¹ and R³², which may be the same or different, represent C₁₋₆ alkyl optionally substituted by mono- or di-C₁₋₆ alkylamino, which may form cyclic amino, or a halogen atom, and the cyclic amino group may contain 1 to 3 heteroatoms, or (iv) R³¹ and R³² together with the carbon atoms to which they are respectively attached form a saturated or unsaturated five- to seven-membered carbocyclic ring,

R⁵ represents formula (IIIb) or formula (IIIc)

wherein

(i) D, E, and J represent a carbon atom, G represents an oxygen or sulfur atom, any one or two of R⁸, R⁹, and R¹⁰, which may be the same or different, represent a halogen atom; hydroxymethyl; C₁₋₆ alkyl optionally substituted by a halogen atom; or C₁₋₆ alkoxy optionally substituted by a halogen atom, and the others represent a hydrogen atom, or (ii) D, E, and J represent a carbon atom, G represents an oxygen or sulfur atom, one of R⁸, R⁹, and R¹⁰ represents a group of formula (IV) wherein Q, X1, and R¹³ are as defined above, or a group of formula (V) wherein X2, X3, R¹⁴, and R¹⁵ are as defined above, and the others represent a hydrogen atom,

Z represents group (A), group (B), or group (C):

wherein

R⁶ represents a hydrogen atom or C₁₋₆ alkyl,

R⁷ represents optionally substituted aryl, optionally substituted aryl C₁₋₆ alkyl, optionally substituted aryl C₂₋₆ alkenyl, or optionally substituted saturated or unsaturated five- or six-membered heterocyclic group, and

R¹⁷ represents a hydrogen atom.

In formula (I-1), more preferably,

A represents formula (IIc)

wherein

(i) R³³ and R³⁴ represent a hydrogen atom, (ii) any one of R³³ and R³⁴ represents a hydrogen atom, and the other represents C₁₋₆ alkyl optionally substituted by mono- or di-C₁₋₆ alkylamino, which may form cyclic amino, or a halogen atom, and the cyclic amino group may contain 1 to 3 heteroatoms, (iii) R³³ and R³⁴, which may be the same or different, represent C₁₋₆ alkyl optionally substituted by mono- or di-C₁₋₆ alkylamino, which may form cyclic amino, or a halogen atom, and the cyclic amino group may contain 1 to 3 heteroatoms, or (iv) R³³ and R³⁴ together with the carbon atoms to which they are respectively attached form a saturated or unsaturated five- to seven-membered carbocyclic ring,

R⁵ represents formula (IIIa)

wherein

(i) D, E, J, L, and M represent a carbon atom, any one or two of R⁸, R⁹, R¹⁰, R¹¹, and R¹², which may be the same or different, represent a halogen atom; hydroxymethyl; C₁₋₆ alkyl optionally substituted by a halogen atom; or C₁₋₆ alkoxy optionally substituted by a halogen atom, and the others represent a hydrogen atom, (ii) any one or two of D, E, J, L, and M represent a nitrogen atom, and the others represent a carbon atom, any one or two of R⁸, R⁹, R¹⁰, R¹¹, and R¹² may be the same or different and represent a halogen atom; hydroxymethyl; C₁₋₆ alkyl optionally substituted by a halogen atom, or C₁₋₆ alkoxy optionally substituted by a halogen atom, and the others represent a hydrogen atom, (iii) D, E, J, L, and M represent a carbon atom, R⁸, R⁹, and R¹² represent a hydrogen atom, any one of R¹⁰ and R¹¹ represents a group of formula (IV) wherein Q, X1, and R¹³ are as defined above, or a group of formula (V) wherein X2, X3, R¹⁴, and R¹⁵ are as defined above, and the other represents a hydrogen atom, or (iv) any one or two of D, E, J, L, and M represent a nitrogen atom, and the others represent a carbon atom, R⁸, R⁹, and R¹² represent a hydrogen atom, and one of R¹⁰ and R¹¹ represents a group of formula (IV) wherein Q, X1, and R¹³ are as defined above, or a group of formula (V) wherein X2, X3, R¹⁴, and R¹⁵ are as defined above, and the other represents a hydrogen atom,

Z represents group (A), group (B), or group (C):

wherein

R⁶ represents a hydrogen atom or C₁₋₆ alkyl,

R⁷ represents optionally substituted aryl, optionally substituted aryl C₁₋₆ alkyl, optionally substituted aryl C₂₋₆ alkenyl, or optionally substituted saturated or unsaturated five- or six-membered heterocyclic group, and

R¹⁷ represents a hydrogen atom.

In formula (I-1), more preferably,

A represents formula (IIc)

wherein

(i) R³³ and R³⁴ represent a hydrogen atom, (ii) any one of R³³ and R³⁴ represents a hydrogen atom, and the other represents C₁₋₆ alkyl optionally substituted by mono- or di-C₁₋₆ alkylamino, which may form cyclic amino, or a halogen atom, and the cyclic amino group may contain 1 to 3 heteroatoms, (iii) R³³ and R³⁴, which may be the same or different, represent C₁₋₆ alkyl optionally substituted by mono- or di-C₁₋₆ alkylamino, which may form cyclic amino, or a halogen atom, and the cyclic amino group may contain 1 to 3 heteroatoms, or (iv) R³³ and R³⁴ together with the carbon atoms to which they are respectively attached form a saturated or unsaturated five- to seven-membered carbocyclic ring,

R⁵ represents formula (IIIb) or formula (IIIc)

wherein

(i) D, E, and J represent a carbon atom, G represents an oxygen or sulfur atom, any one or two of R⁸, R⁹, and R¹⁰, which may be the same or different, represent a halogen atom; hydroxymethyl; C₁₋₆ alkyl optionally substituted by a halogen atom; or C₁₋₆ alkoxy optionally substituted by a halogen atom, and the others represent a hydrogen atom, or (ii) D, E, and J represent a carbon atom, G represents an oxygen or sulfur atom, one of R⁶, R⁹, and R¹⁰ represents a group of formula (IV) wherein Q, X1, and R¹³ are as defined above, or a group of formula (V) wherein X2, X3, R¹⁴, and R¹⁵ are as defined above, and the others represent a hydrogen atom,

Z represents group (A), group (B), or group (C):

wherein

R⁶ represents a hydrogen atom or C₁₋₆ alkyl,

R⁷ represents optionally substituted aryl, optionally substituted aryl C₁₋₆ alkyl, optionally substituted aryl C₂₋₆ alkenyl, or optionally substituted saturated or unsaturated five- or six-membered heterocyclic group, and

R¹⁷ represents a hydrogen atom.

In formula (I-1), more preferably,

A represents formula (IId)

wherein R³⁵ and R³⁶ represent a hydrogen atom, or any one of R³⁵ and R³⁶ represents a hydrogen atom with the other representing C₁₋₆ alkyl optionally substituted by a halogen atom,

R⁵ represents formula (IIIa)

wherein

(i) D, E, J, L, and M represent a carbon atom, any one or two of R⁸, R⁹, R¹⁰, R¹¹, and R¹², which may be the same or different, represent a halogen atom; hydroxymethyl; C₁₋₆ alkyl optionally substituted by a halogen atom; or C₁₋₆ alkoxy optionally substituted by a halogen atom, and the others represent a hydrogen atom, (ii) any one or two of D, E, J, L, and M represent a nitrogen atom, and the others represent a carbon atom, any one or two of R⁸, R⁹, R¹⁰, R¹¹, and R¹² may be the same or different and represent a halogen atom; hydroxymethyl; C₁₋₆ alkyl optionally substituted by a halogen atom, or C₁₋₆ alkoxy optionally substituted by a halogen atom, and the others represent a hydrogen atom, (iii) D, E, J, L, and M represent a carbon atom, R⁸, R⁹, and R¹² represent a hydrogen atom, any one of R¹⁰ and R¹¹ represents a group of formula (IV) wherein Q, X1, and R¹³ are as defined above, or a group of formula (V) wherein X2, X3, R¹⁴, and R¹⁵ are as defined above, and the other represents a hydrogen atom, or (iv) any one or two of D, E, J, L, and M represent a nitrogen atom, and the others represent a carbon atom, R⁸, R⁹, and R¹² represent a hydrogen atom, and one of R¹⁰ and R¹¹ represents a group of formula (IV) wherein Q, X1, and R¹³ are as defined above, or a group of formula (V) wherein X2, X3, R¹⁴, and R¹⁵ are as defined above, and the other represents a hydrogen atom,

Z represents group (A), group (B), or group (C):

wherein

R⁶ represents a hydrogen atom or C₁₋₆ alkyl,

R⁷ represents optionally substituted aryl, optionally substituted aryl C₁₋₆ alkyl, optionally substituted aryl C₂₋₆ alkenyl, or optionally substituted saturated or unsaturated five- or six-membered heterocyclic group, and

R¹⁷ represents a hydrogen atom.

In formula (I-1), more preferably,

A represents formula (IId)

wherein R³⁵ and R³⁶ represent a hydrogen atom, or any one of R³⁵ and R³⁶ represents a hydrogen atom with the other representing C₁₋₆ alkyl optionally substituted by a halogen atom,

R⁵ represents formula (IIIb) or formula (IIIc)

wherein

(i) D, E, and J represent a carbon atom, G represents an oxygen or sulfur atom, any one or two of R⁸, R⁹, and R¹⁰, which may be the same or different, represent a halogen atom; hydroxymethyl; C₁₋₆ alkyl optionally substituted by a halogen atom; or C₁₋₆ alkoxy optionally substituted by a halogen atom, and the others represent a hydrogen atom, or (ii) D, E, and J represent a carbon atom, G represents an oxygen or sulfur atom, one of R⁸, R⁹, and R¹⁰ represents a group of formula (IV) wherein Q, X1, and R¹³ are as defined above, or a group of formula (V) wherein X2, X3, R¹⁴, and R¹⁵ are as defined above, and the others represent a hydrogen atom,

Z represents group (A), group (B), or group (C):

wherein

R⁶ represents a hydrogen atom or C₁₋₆ alkyl,

R⁷ represents optionally substituted aryl, optionally substituted aryl C₁₋₆ alkyl, optionally substituted aryl C₂₋₆ alkenyl, or optionally substituted saturated or unsaturated five- or six-membered heterocyclic group, and

R¹⁷ represents a hydrogen atom.

Among the compounds of formula (I), quinazolone derivatives may be represented by formula (I-2).

wherein A, R⁵, Z, and

are as defined in formula (I).

In formula (I-2), preferably,

A represents formula (IIa) or formula (IIa′) wherein R¹, R², R³, and R⁴ are as defined in formula (IIa) and formula (IIa′) and are preferably the same or different and represent a hydrogen atom; a halogen atom; hydroxyl; optionally substituted C₁₋₆ alkyl; or optionally substituted C₁₋₆ alkoxy,

R⁵ represents optionally substituted C₅₋₇ cycloalkyl, optionally substituted aryl, preferably phenyl, or optionally substituted saturated or unsaturated five- or six-membered heterocyclic group, preferably pyridyl, thienyl, isoxazole, or pyrimidyl and more preferably represents a group of formula (IIIa), formula (IIIb) or formula (IIIc).

Z represents group (A), group (B), or group (C) wherein R⁶ represents a hydrogen atom or C₁₋₆ alkyl, R⁷ represents optionally substituted aryl, preferably, phenyl, or naphthyl, optionally substituted aryl, preferably phenyl, or naphthyl, C₁₋₆ alkyl, optionally substituted aryl, preferably phenyl, or naphthyl, C₂₋₆ alkenyl, or optionally substituted saturated or unsaturated five- or six-membered heterocyclic group, preferably furyl, thienyl, pyrrolyl, or pyridyl, and R¹⁷ represents a hydrogen atom.

In formula (I-2), preferably,

A represents formula (IIa) wherein R¹, R², R³, and R⁴ are as defined in formula (IIa),

represents a double bond,

R⁵ represents optionally substituted C₅₋₇ cycloalkyl, optionally substituted aryl, or optionally substituted saturated or unsaturated five- or six-membered heterocyclic group, preferably pyridyl, thienyl, isoxazole, or pyrimidyl and more preferably represents a group of formula (IIIa), formula (IIIb), or formula (IIIc).

Z represents group (A) or group (B) wherein R⁶ represents a hydrogen atom or C₁₋₆ alkyl, R⁷ represents optionally substituted aryl, preferably phenyl, optionally substituted aryl C₁₋₆ alkyl, optionally substituted aryl C₂₋₆ alkenyl, or optionally substituted saturated or unsaturated five- or six-membered heterocyclic group, and R¹⁷ represents a hydrogen atom.

In formula (I-2), preferably,

A represents formula (IIb) wherein R³¹ and R³² are as defined in formula (IIb), preferably, R³¹ and R³² represent a hydrogen atom, or any one of R³¹ and R³² represents a hydrogen atom with the other representing C₁₋₆ alkyl optionally substituted by a halogen atom, or R³¹ and R³² together may form a C₃₋₅ alkylene chain,

R⁵ represents optionally substituted C₆₋₇ cycloalkyl, optionally substituted aryl, preferably phenyl, or optionally substituted saturated or unsaturated five- or six-membered heterocyclic group, preferably pyridyl, thienyl, isoxazole, or pyrimidyl, more preferably a group of formula (IIIa), formula (IIIb), or formula (IIIc), and

Z represents group (A) or group (B) wherein R⁶ represents a hydrogen atom or C₁₋₆ alkyl, R⁷ represents optionally substituted aryl, optionally substituted aryl C₁₋₆ alkyl, optionally substituted aryl C₂₋₆ alkenyl, or optionally substituted saturated or unsaturated five- or six-membered heterocyclic group, and R¹⁷ represents a hydrogen atom.

In formula (I-2), preferably,

A represents formula (IIc) wherein R³³ and R³⁴ are as defined in formula (IIc), and, preferably, R³³ and R³⁴ represent a hydrogen atom, or any one of R³³ and R³⁴ represents a hydrogen atom with the other representing C₁₋₆ alkyl optionally substituted by a halogen atom, or R³³ and R³⁴ together form a C₃₋₅ alkylene chain,

R⁵ represents optionally substituted C₅₋₇ cycloalkyl, optionally substituted aryl, preferably phenyl, or optionally substituted saturated or unsaturated five- or six-membered heterocyclic group, preferably pyridyl, thienyl, isoxazole, or pyrimidyl, more preferably a group of formula (IIIa), formula (IIIb), or formula (IIIc), and

Z represents group (A) and group (B) wherein R⁶ represents a hydrogen atom or C₁₋₆ alkyl, R⁷ represents optionally substituted aryl, optionally substituted aryl C₁₋₆ alkyl, optionally substituted aryl C₂₋₆ alkenyl, or optionally substituted saturated or unsaturated five- or six-membered heterocyclic group, and R¹⁷ represents a hydrogen atom.

In formula (I-2), preferably,

A represents formula (IId) wherein R³⁵ and R³⁶ are as defined in formula (IId), and R³⁵ and R³⁶ represent a hydrogen atom, or any one of R³⁵ and R³⁶ represents a hydrogen atom with the other representing C₁₋₆ alkyl optionally substituted by a halogen atom,

R⁵ represents optionally substituted C₅₋₇ cycloalkyl, optionally substituted aryl, preferably phenyl, or optionally substituted saturated or unsaturated five- or six-membered heterocyclic group, preferably pyridyl, thienyl, isoxazole, or pyrimidyl, more preferably a group of formula (IIIa), formula (IIIb), or formula (IIIc),

Z represents group (A) or group (B) wherein R⁶ represents a hydrogen atom or C₁₋₆ alkyl, R⁷ represents optionally substituted aryl, optionally substituted aryl C₁₋₆ alkyl, optionally substituted aryl C₂₋₆ alkenyl, or optionally substituted saturated or unsaturated five- or six-membered heterocyclic group, and R¹⁷ represents a hydrogen atom.

In formula (I-2), more preferably,

A represents formula (IIa) or formula (IIa′),

wherein

(1) R¹, R², R³, and R⁴ represent a hydrogen atom, (2) R¹ and R⁴ represent a hydrogen atom, any one of R² and R³ represents a halogen atom; hydroxyl; optionally substituted C₁₋₆ alkyl; optionally substituted C₁₋₆ alkoxy; optionally substituted mono- or di-arylamino; optionally substituted mono- or di-C₁₋₆ alkylamino in which the dialkylamino together may form optionally substituted cyclic amino optionally containing 1 to 3 heteroatoms; or optionally substituted mono- or di-C₂₋₆ alkenylamino in which the di-C₂₋₆ alkenylamino group together may form optionally substituted unsaturated cyclic amino optionally containing 1 to 3 heteroatoms, and the other represents a hydrogen atom, (3) R¹ and R⁴ represent a hydrogen atom, and R² and R³, which may be the same or different, represent a halogen atom; hydroxyl; optionally substituted C₁₋₆ alkyl; or optionally substituted C₁₋₆ alkoxy, (4) R¹ and R⁴ represent a hydrogen atom, and R² and R³ together with the carbon atoms to which they are respectively attached form a saturated or unsaturated five- to seven-membered carbocyclic ring, (5) R¹ and R⁴ represent a hydrogen atom, any one of R² and R³ represents optionally substituted mono- or di-C₁₋₆ alkylamino in which the di-C₁₋₆ alkylamino together may form optionally substituted cyclic amino optionally containing 1 to 3 heteroatoms, and the other represents a hydrogen atom, or (6) R¹ and R⁴ represent a hydrogen atom, any one of R² and R³ represents optionally substituted C₁₋₆ alkoxy, and the other represents a hydrogen atom,

R⁵ represents formula (IIIa)

wherein

(i) D, E, J, L, and M represent a carbon atom, any one or two of R⁸, R⁹, R¹⁰, R¹¹, and R¹², which may be the same or different, represent a halogen atom; hydroxymethyl; C₁₋₆ alkyl optionally substituted by a halogen atom; or C₁₋₆ alkoxy optionally substituted by a halogen atom, and the others represent a hydrogen atom, (ii) any one or two of D, E, J, L, and M represent a nitrogen atom, and the others represent a carbon atom, any one or two of R⁸, R⁹, R¹⁰, R¹¹, and R¹² may be the same or different and represent a halogen atom; hydroxymethyl; C₁₋₆ alkyl optionally substituted by a halogen atom, or C₁₋₆ alkoxy optionally substituted by a halogen atom, and the others represent a hydrogen atom, (iii) D, E, J, L, and M represent a carbon atom, R⁸, R⁹, and R¹² represent a hydrogen atom, any one of R¹⁰ and R¹¹ represents a group of formula (IV) wherein Q, X1, and R¹³ are as defined above, or a group of formula (V) wherein X2, X3, R¹⁴, and R¹⁵ are as defined above, and the other represents a hydrogen atom, (iv) any one or two of D, E, J, L, and M represent a nitrogen atom, and the others represent a carbon atom, R⁸, R⁹, and R¹² represent a hydrogen atom, and one of R¹⁰ and R¹¹ represents a group of formula (IV) wherein Q, X1, and R¹³ are as defined above, or a group of formula (V) wherein X2, X3, R¹⁴, and R¹⁵ are as defined above, and the other represents a hydrogen atom,

Z represents group (A), group (B), or group (C):

wherein

R⁶ represents a hydrogen atom or C₁₋₆ alkyl,

R⁷ represents optionally substituted aryl, optionally substituted aryl C₁₋₆ alkyl, optionally substituted aryl C₂₋₆ alkenyl, or optionally substituted saturated or unsaturated five- or six-membered heterocyclic group, and

R¹⁷ represents a hydrogen atom.

In formula (I-2), more preferably,

A represents formula (IIa) or formula (IIa′)

wherein

(1) R¹, R², R³, and R⁴ represent a hydrogen atom, (2) R¹ and R⁴ represent a hydrogen atom, any one of R² and R³ represents a halogen atom; hydroxyl; optionally substituted C₁₋₆ alkyl; optionally substituted C₁₋₆ alkoxy; optionally substituted mono- or di-arylamino; optionally substituted mono- or di-C₁₋₆ alkylamino in which the dialkylamino together may form optionally substituted cyclic amino optionally containing 1 to 3 heteroatoms; or optionally substituted mono- or di-C₂₋₆ alkenylamino in which the di-C₂₋₆ alkenylamino group together may form optionally substituted unsaturated cyclic amino optionally containing 1 to 3 heteroatoms, and the other represents a hydrogen atom, (3) R¹ and R⁴ represent a hydrogen atom, and R² and R³, which may be the same or different, represent a halogen atom; hydroxyl; optionally substituted C₁₋₆ alkyl; or optionally substituted C₁₋₆ alkoxy, (4) R¹ and R⁴ represent a hydrogen atom, and R² and R³ together with the carbon atoms to which they are respectively attached form a saturated or unsaturated five- to seven-membered carbocyclic ring, (5) R¹ and R⁴ represent a hydrogen atom, any one of R² and R³ represents optionally substituted mono- or di-C₁₋₆ alkylamino in which the di-C₁₋₆ alkylamino together may form optionally substituted cyclic amino optionally containing 1 to 3 heteroatoms, and the other represents a hydrogen atom, or (6) R¹ and R⁴ represent a hydrogen atom, any one of R² and R³ represents optionally substituted C₁₋₆ alkoxy, and the other represents a hydrogen atom,

R⁵ represents formula (IIIb) or formula (IIIc)

wherein

(i) D, E, and J represent a carbon atom, G represents an oxygen or sulfur atom, any one or two of R⁸, R⁹, and R¹⁰, which may be the same or different, represent a halogen atom; hydroxymethyl; C₁₋₆ alkyl optionally substituted by a halogen atom; or C₁₋₆ alkoxy optionally substituted by a halogen atom, and the others represent a hydrogen atom, or (ii) D, E, and J represent a carbon atom, G represents an oxygen or sulfur atom, one of R⁸, R⁹, and R¹⁰ represents a group of formula (IV) wherein Q, X1, and R¹³ are as defined above, or a group of formula (V) wherein X2, X3, R¹⁴, and R¹⁵ are as defined above, and the others represent a hydrogen atom,

Z represents group (A), group (B), or group (C):

wherein

R⁶ represents a hydrogen atom or C₁₋₆ alkyl,

R⁷ represents optionally substituted aryl, optionally substituted aryl C₁₋₆ alkyl, optionally substituted aryl C₂₋₆ alkenyl, or optionally substituted saturated or unsaturated five- or six-membered heterocyclic group, and

R¹⁷ represents a hydrogen atom.

In formula (I-2), more preferably,

A represents formula (IIb)

wherein

(i) R³¹ and R³² represent a hydrogen atom, (ii) any one of R³¹ and R³² represents a hydrogen atom, and the other represents C₁₋₆ alkyl optionally substituted by mono- or di-C₁₋₆ alkylamino, which may form cyclic amino, or a halogen atom, and the cyclic amino group may contain 1 to 3 heteroatoms, (iii) R³¹ and R³², which may be the same or different, represent C₁₋₆ alkyl optionally substituted by mono- or di-C₁₋₆ alkylamino, which may form cyclic amino, or a halogen atom, and the cyclic amino group may contain 1 to 3 heteroatoms, or (iv) R³¹ and R³² together with the carbon atoms to which they are respectively attached form a saturated or unsaturated five- to seven-membered carbocyclic ring,

R⁵ represents formula (IIIa)

wherein

(i) D, E, J, L, and M represent a carbon atom, any one or two of R⁸, R⁹, R¹⁰, R¹¹, and R¹², which may be the same or different, represent a halogen atom; hydroxymethyl; C₁₋₆ alkyl optionally substituted by a halogen atom; or C₁₋₆ alkoxy optionally substituted by a halogen atom, and the others represent a hydrogen atom, (ii) any one or two of D, E, J, L, and M represent a nitrogen atom, and the others represent a carbon atom, any one or two of R⁸, R⁹, R¹⁰, R¹¹, and R¹² may be the same or different and represent a halogen atom; hydroxymethyl; C₁₋₆ alkyl optionally substituted by a halogen atom, or C₁₋₆ alkoxy optionally substituted by a halogen atom, and the others represent a hydrogen atom, (iii) D, E, J, L, and M represent a carbon atom, R⁸, R⁹, and R¹² represent a hydrogen atom, any one of R¹⁰ and R¹¹ represents a group of formula (IV) wherein Q, X1, and R¹³ are as defined above, or a group of formula (V) wherein X2, X3, R¹⁴, and R¹⁵ are as defined above, and the other represents a hydrogen atom, or (iv) any one or two of D, E, J, L, and M represent a nitrogen atom, and the others represent a carbon atom, R⁸, R⁹, and R¹² represent a hydrogen atom, and one of R¹⁰ and R¹¹ represents a group of formula (IV) wherein Q, X1, and R¹³ are as defined above, or a group of formula (V) wherein X2, X3, R¹⁴, and R¹⁵ are as defined in above, and the other represents a hydrogen atom,

Z represents group (A), group (B), or group (C):

wherein

R⁶ represents a hydrogen atom or C₁₋₆ alkyl,

R⁷ represents optionally substituted aryl, optionally substituted aryl C₁₋₆ alkyl, optionally substituted aryl C₂₋₆ alkenyl, or optionally substituted saturated or unsaturated five- or six-membered heterocyclic group, and

R¹⁷ represents a hydrogen atom.

In formula (I-2), more preferably,

A represents formula (IIb)

wherein

(i) R³¹ and R³² represent a hydrogen atom, (ii) any one of R³¹ and R³² represents a hydrogen atom, and the other represents C₁₋₆ alkyl optionally substituted by mono- or di-C₁₋₆ alkylamino, which may form cyclic amino, or a halogen atom, and the cyclic amino group may contain 1 to 3 heteroatoms, (iii) R³¹ and R³², which may be the same or different, represent C₁₋₆ alkyl optionally substituted by mono- or di-C₁₋₆ alkylamino, which may form cyclic amino, or a halogen atom, and the cyclic amino group may contain 1 to 3 heteroatoms, or (iv) R³¹ and R³² together with the carbon atoms to which they are respectively attached form a saturated or unsaturated five- to seven-membered carbocyclic ring,

R⁵ represents formula (IIIb) or formula (IIIc)

wherein

(i) D, E, and J represent a carbon atom, G represents an oxygen or sulfur atom, any one or two of R⁸, R⁹, and R¹⁰, which may be the same or different, represent a halogen atom; hydroxymethyl; C₁₋₆ alkyl optionally substituted by a halogen atom; or C₁₋₆ alkoxy optionally substituted by a halogen atom, and the others represent a hydrogen atom, or (ii) D, E, and J represent a carbon atom, G represents an oxygen or sulfur atom, one of R⁸, R⁹, and R¹⁰ represents a group of formula (IV) wherein Q, X1, and R¹³ are as defined above, or a group of formula (V) wherein X2, X3, R¹⁴, and R¹⁵ are as defined above, and the others represent a hydrogen atom,

Z represents group (A), group (B), or group (C):

wherein

R⁶ represents a hydrogen atom or C₁₋₆ alkyl,

R⁷ represents optionally substituted aryl, optionally substituted aryl C₁₋₆ alkyl, optionally substituted aryl C₂₋₆ alkenyl, or optionally substituted saturated or unsaturated five- or six-membered heterocyclic group, and

R¹⁷ represents a hydrogen atom.

In formula (I-2), more preferably,

A represents formula (IIc)

wherein

(i) R³³ and R³⁴ represent a hydrogen atom, (ii) any one of R³³ and R³⁴ represents a hydrogen atom, and the other represents C₁₋₆ alkyl optionally substituted by mono- or di-C₁₋₆ alkylamino, which may form cyclic amino, or a halogen atom, and the cyclic amino group may contain 1 to 3 heteroatoms, (iii) R³³ and R³⁴, which may be the same or different, represent C₁₋₆ alkyl optionally substituted by mono- or di-C₁₋₆ alkylamino, which may form cyclic amino, or a halogen atom, and the cyclic amino group may contain 1 to 3 heteroatoms, or (iv) R³³ and R³⁴ together with the carbon atoms to which they are respectively attached form a saturated or unsaturated five- to seven-membered carbocyclic ring,

R⁵ represents formula (IIIa)

wherein

(i) D, E, J, L, and M represent a carbon atom, any one or two of R⁸, R⁹, R¹⁰, R¹¹, and R¹², which may be the same or different, represent a halogen atom; hydroxymethyl; C₁₋₆ alkyl optionally substituted by a halogen atom; or C₁₋₆ alkoxy optionally substituted by a halogen atom, and the others represent a hydrogen atom, (ii) any one or two of D, E, J, L, and M represent a nitrogen atom, and the others represent a carbon atom, any one or two of R⁸, R⁹, R¹⁰, R¹¹, and R¹² may be the same or different and represent a halogen atom; hydroxymethyl; C₁₋₆ alkyl optionally substituted by a halogen atom, or C₁₋₆ alkoxy optionally substituted by a halogen atom, and the others represent a hydrogen atom, (iii) D, E, J, L, and M represent a carbon atom, R⁸, R⁹, and R¹² represent a hydrogen atom, any one of R¹⁰ and R¹¹ represents a group of formula (IV) wherein Q, X1, and R¹³ are as defined above, or a group of formula (V) wherein X2, X3, R¹⁴, and R¹⁵ are as defined above, and the other represents a hydrogen atom, or (iv) any one or two of D, E, J, L, and M represent a nitrogen atom, and the others represent a carbon atom, R⁸, R⁹, and R¹² represent a hydrogen atom, and one of R¹⁰ and R¹¹ represents a group of formula (IV) wherein Q, X1, and R¹³ are as defined above, or a group of formula (V) wherein X2, X3, R¹⁴, and R¹⁵ are as defined above, and the other represents a hydrogen atom,

Z represents group (A), group (B), or group (C):

wherein

R⁶ represents a hydrogen atom or C₁₋₆ alkyl,

R⁷ represents optionally substituted aryl, optionally substituted aryl C₁₋₆ alkyl, optionally substituted aryl C₂₋₆ alkenyl, or optionally substituted saturated or unsaturated five- or six-membered heterocyclic group, and

R¹⁷ represents a hydrogen atom.

In formula (I-2), more preferably,

A represents formula (IIc)

wherein

(i) R³³ and R³⁴ represent a hydrogen atom, (ii) any one of R³³ and R³⁴ represents a hydrogen atom, and the other represents C₁₋₆ alkyl optionally substituted by mono- or di-C₁₋₆ alkylamino, which may form cyclic amino, or a halogen atom, and the cyclic amino group may contain 1 to 3 heteroatoms, (iii) R³³ and R³⁴, which may be the same or different, represent C₁₋₆ alkyl optionally substituted by mono- or di-C₁₋₆ alkylamino, which may form cyclic amino, or a halogen atom, and the cyclic amino group may contain 1 to 3 heteroatoms, or (iv) R³³ and R³⁴ together with the carbon atoms to which they are respectively attached form a saturated or unsaturated five- to seven-membered carbocyclic ring,

R⁵ represents formula (IIIb) or formula (IIIc)

wherein

(i) D, E, and J represent a carbon atom, G represents an oxygen or sulfur atom, any one or two of R⁸, R⁹, and R¹⁰, which may be the same or different, represent a halogen atom; hydroxymethyl; C₁₋₆ alkyl optionally substituted by a halogen atom; or C₁₋₆ alkoxy optionally substituted by a halogen atom, and the others represent a hydrogen atom, or (ii) D, E, and J represent a carbon atom, G represents an oxygen or sulfur atom, one of R⁸, R⁹, and R¹⁰ represents a group of formula (IV) wherein Q, X1, and R¹³ are as defined above, or a group of formula (V) wherein X2, X3, R¹⁴, and R¹⁵ are as defined above, and the others represent a hydrogen atom,

Z represents group (A), group (B), or group (C):

wherein

R⁶ represents a hydrogen atom or C₁₋₆ alkyl,

R⁷ represents optionally substituted aryl, optionally substituted aryl C₁₋₆ alkyl, optionally substituted aryl C₂₋₆ alkenyl, or optionally substituted saturated or unsaturated five- or six-membered heterocyclic group, and

R¹⁷ represents a hydrogen atom.

In formula (I-2), more preferably,

A represents formula (IId)

wherein R³⁵ and R³⁶ represent a hydrogen atom, or any one of R³⁵ and R³⁶ represents a hydrogen atom with the other representing C₁₋₆ alkyl optionally substituted by a halogen atom,

R⁵ represents formula (IIIa)

wherein

(i) D, E, J, L, and M represent a carbon atom, any one or two of R⁸, R⁹, R¹⁰, R¹¹, and R¹², which may be the same or different, represent a halogen atom; hydroxymethyl; C₁₋₆ alkyl optionally substituted by a halogen atom; or C₁₋₆ alkoxy optionally substituted by a halogen atom, and the others represent a hydrogen atom, (ii) any one or two of D, E, J, L, and M represent a nitrogen atom, and the others represent a carbon atom, any one or two of R⁸, R⁹, R¹⁰, R¹¹, and R¹² may be the same or different and represent a halogen atom; hydroxymethyl; C₁₋₆ alkyl optionally substituted by a halogen atom, or C₁₋₆ alkoxy optionally substituted by a halogen atom, and the others represent a hydrogen atom, (iii) D, E, J, L, and M represent a carbon atom, R⁸, R⁹, and R¹² represent a hydrogen atom, any one of R¹⁰ and R¹¹ represents a group of formula (IV) wherein Q, X1, and R¹³ are as defined above, or a group of formula (V) wherein X2, X3, R¹⁴, and R¹⁵ are as defined above, and the other represents a hydrogen atom, or (iv) any one or two of D, E, J, L, and M represent a nitrogen atom, and the others represent a carbon atom, R⁸, R⁹, and R¹² represent a hydrogen atom, and one of R¹⁰ and R¹¹ represents a group of formula (IV) wherein Q, X1, and R¹³ are as defined above, or a group of formula (V) wherein X2, X3, R¹⁴, and R¹⁵ are as defined above, and the other represents a hydrogen atom,

Z represents group (A), group (B), or group (C):

wherein

R⁶ represents a hydrogen atom or C₁₋₆ alkyl,

R⁷ represents optionally substituted aryl, optionally substituted aryl C₁₋₆ alkyl, optionally substituted aryl C₂₋₆ alkenyl, or optionally substituted saturated or unsaturated five- or six-membered heterocyclic group, and

R¹⁷ represents a hydrogen atom.

In formula (I-2), more preferably,

A represents formula (IId)

wherein R³⁵ and R³⁶ represent a hydrogen atom, or any one of R³⁵ and R³⁶ represents a hydrogen atom with the other representing C₁₋₆ alkyl optionally substituted by a halogen atom,

R⁵ represents formula (IIIb) or formula (IIIc)

wherein

(i) D, E, and J represent a carbon atom, G represents an oxygen or sulfur atom, any one or two of R⁸, R⁹, and R¹⁰, which may be the same or different, represent a halogen atom; hydroxymethyl; C₁₋₆ alkyl optionally substituted by a halogen atom; or C₁₋₆ alkoxy optionally substituted by a halogen atom, and the others represent a hydrogen atom, or (ii) D, E, and J represent a carbon atom, G represents an oxygen or sulfur atom, one of R⁸, R⁹, and R¹⁰ represents a group of formula (IV) wherein Q, X1, and R¹³ are as defined above, or a group of formula (V) wherein X2, X3, R¹⁴, and R¹⁵ are as defined above, and the others represent a hydrogen atom,

Z represents group (A), group (B), or group (C):

wherein

R⁶ represents a hydrogen atom or C₁₋₆ alkyl,

R⁷ represents optionally substituted aryl, optionally substituted aryl C₁₋₆ alkyl, optionally substituted aryl C₂₋₆ alkenyl, or optionally substituted saturated or unsaturated five- or six-membered heterocyclic group, and

R¹⁷ represents a hydrogen atom.

Examples of preferred compounds according to the present invention include compounds 1 to 1077 described in the Examples.

Compounds of formula (I) according to the present invention include compounds wherein

A represents a five- to nine-membered unsaturated carbocyclic moiety or a five- to nine-membered unsaturated heterocyclic moiety, and

represents a double bond,

the carbocyclic moiety and heterocyclic moiety represented by A are optionally substituted by

(a) a halogen atom;

(b) hydroxyl;

(c) C₁₋₆ alkyl;

(d) C₁₋₆ alkoxy;

(e) aryl;

(f) aryloxy;

(g) arylthio;

(h) alkylthio;

(i) nitro; or

(j) amino,

(c) the C₁₋₆ alkyl group, (d) the C₁₋₆ alkoxy group, (e) the aryl group, (f) the aryloxy group, (g) the arylthio group, and (h) the alkylthio group are optionally substituted by (1) hydroxyl, (2) thiol, (3) amino, (4) C₁₋₆ alkoxy, (5) C₁₋₆ alkylthio, (6) C₁₋₆ alkylsulfonyl, (7) mono- or di-C₁₋₆ alkylamino in which the di-C₁₋₆ alkylamino group may form cyclic amino optionally containing 1 to 3 heteroatoms, (8) aryloxy, (9) arylthio, (10) arylsulfonyl, (11) aryl, (12) a heterocyclic group, (13) a halogen atom, or (14) arylamino in which the amino group is optionally substituted by C₁₋₆ alkyl, and the aryl group is optionally substituted by a halogen atom, C₁₋₆ alkyl, C₁₋₆ alkoxy, or C₁₋₆ alkylamino,

when the carbocyclic moiety and the heterocyclic moiety are substituted by two (c) C₁₋₆ alkyl groups, they together may form a C₃₋₅ alkylene chain,

R⁵ represents C₁₋₆ alkyl, aryl, C₁₋₆ alkoxy, aryloxy, C₁₋₆ alkylamino, arylamino, C₁₋₆ alkylthio, arylthio, C₃₋₇ cycloalkyl, or a heterocyclic group, and the C₁₋₆ alkyl, aryl, C₁₋₆ alkoxy, aryloxy, C₁₋₆ alkylamino, arylamino, C₁₋₆ alkylthio, arylthio, C₃₋₇ cycloalkyl, or heterocyclic group represented by R⁵ may be the same or different, and is optionally substituted by

(I) a halogen atom;

(II) C₁₋₆ alkyl optionally containing a substituent selected from the group consisting of (1) hydroxyl, (2) thiol, (3) amino, (4) C₁₋₆ alkoxy, (5) C₁₋₆ alkylthio, (6) C₁₋₆ alkylsulfinyl, (7) C₁₋₆ alkylsulfonyl, (8) mono- or di-C₁₋₆ alkylamino, (8′) amino substituted by a heterocyclic group optionally substituted by C₁₋₆ alkyl, (9) C₁₋₆ alkylcarbonyloxy, (10) C₁₋₆ alkylcarbonylthio, (11) C₁₋₆ alkylcarbonylamino, (12) aryloxy, (13) arylthio, (14) arylsulfinyl, (15) arylsulfonyl, (16) arylamino, (17) C₁₋₆ alkyl- or aryl-sulfonylamino, (18) C₁₋₆ alkyl- or aryl-ureido, (19) C₁₋₆ alkoxy- or aryloxy-carbonylamino, (20) C₁₋₆ alkylamino- or arylamino-carbonyloxy, (21) carboxyl, (22) nitro, (23) a heterocyclic group, (23′) Het-S(═O)j- wherein Het represents a heterocyclic group, j is 0, 1, or 2, and Het is optionally substituted by alkyl optionally substituted by mono- or di-C₁₋₆ alkylamino in which the di-C₁₋₆ alkylamino group may form cyclic amino optionally containing 1 to 3 heteroatoms and one or two alkyl groups on the amino group and the cyclic amino moiety are optionally substituted by hydroxyl, (24) cyano, and (25) a halogen atom,

wherein the alkyl moiety in (4) the C₁₋₆ alkoxy group, (5) the C₁₋₆ alkylthio group, (6) the C₁₋₆ alkylsulfinyl group, and (7) the C₁₋₆ alkylsulfonyl group is optionally substituted by a halogen atom; C₁₋₆ alkyl; C₁₋₆ alkoxy; C₁₋₆ alkylthio; mono- or di-C₁₋₆ alkylamino in which the di-C₁₋₆ alkylamino group may form cyclic amino optionally containing 1 to 3 heteroatoms; aryloxy; arylthio; hydroxyl; carboxyl; —S(═O)₂(—OH); C₁₋₆ alkoxy- or aryloxy-carbonyl; C₁₋₆ alkylcarbonyl; aryl; or a heterocyclic group optionally substituted by alkyl optionally substituted by mono- or di-C₁₋₆ alkylamino in which the di-C₁₋₆ alkylamino group may form cyclic amino optionally containing 1 to 3 heteroatoms, and one or two alkyl groups on the amino group and the cyclic amino moiety are optionally substituted by hydroxy, and in (8) the mono- or di-C₁₋₆ alkylamino group, the di-C₁₋₆ alkylamino group may form cyclic amino optionally containing 1 to 3 heteroatoms, and one or two alkyl groups on the amino group and the cyclic amino moiety are optionally substituted by a halogen atom; C₁₋₆ alkyl optionally substituted by hydroxyl; C₁₋₆ alkoxy; C₁₋₆ alkylthio; mono- or di-C₁₋₆ alkylamino in which one or two alkyl groups on the amino group are optionally substituted by hydroxyl; arylamino in which the amino group is optionally substituted by C₁₋₆ alkyl; mono- or di-C₁₋₆ alkylcarbamoylmethyl in which the di-C₁₋₆ alkylamino group may form cyclic amino optionally containing 1 to 3 heteroatoms, and one or two alkyl groups on the amino group and the cyclic amino moiety are optionally substituted by hydroxyl; aryloxy; arylthio; an oxygen atom; hydroxyl; carboxyl; C₁₋₆ alkoxy- or aryloxy-carbonyl; C₁₋₆ alkylcarbonyl; aryl optionally substituted by a halogen atom or hydroxyl; or a heterocyclic group;

(III) C₁₋₆ alkoxy optionally substituted by a halogen atom;

(IV) C₁₋₆ alkylthio optionally substituted by a halogen atom;

(V) C₃₋₇ cycloalkyl;

(VI) aryl;

(VII) aryloxy;

(VIII) C₁₋₆ alkylcarbonylamino;

(VIX) C₁₋₆ alkylcarbonyloxy;

(X) hydroxyl;

(XI) nitro;

(XII) cyano;

(XIII) amino;

(XIV) mono- or di-C₁₋₆ alkylamino in which the di-C₁₋₆ alkylamino group may form cyclic amino optionally containing 1 to 3 heteroatoms;

(XV) arylamino;

(XVI) C₁₋₆ alkyl- or aryl-sulfonylamino;

(XVII) C₁₋₆ alkyl- or aryl-ureido;

(XVIII) C₁₋₆ alkoxy- or aryloxy-carbonylamino;

(XIX) C₁₋₆ alkylamino- or arylamino-carbonyloxy;

(XX) C₁₋₆ alkoxy- or aryloxy-carbonyl;

(XXI) acyl;

(XXII) carboxyl;

(XXIII) carbamoyl;

(XXIV) mono- or di-alkylcarbamoyl;

(XXV) a heterocyclic group;

(XXVI) alkyl- or aryl-sulfonyl;

(XXVII) C₂₋₆ alkenyloxy; or

(XXVIII) C₂₋₆ alkynyloxy,

Z represents group A or group B wherein R⁶, R⁷, and R¹⁷ are as defined in formula (I),

R¹⁰¹ and R¹⁰² together represent ═O, and R¹⁰³ and R¹⁰⁴ represent a hydrogen atom, or R¹⁰¹ and R¹⁰⁴ together represent a bond, and R¹⁰² and R¹⁰³ together represent a bond.

Compounds according to the present invention may form pharmaceutically acceptable salts thereof. Preferred examples of such salts include: alkali metal or alkaline earth metal salts such as sodium salts, potassium salts or calcium salts; hydrohalogenic acid salts such as hydrofluoride salts, hydrochloride salts, hydrobromide salts, or hydroiodide salts; inorganic acid salts such as nitric acid salts, perchloric acid salts, sulfuric acid salts, or phosphoric acid salts; lower alkylsulfonic acid salts such as methanesulfonic acid salts, trifluoromethanesulfonic acid salts, or ethanesulfonic acid salts; arylsulfonic acid salts such as benzenesulfonic acid salts or p-toluenesulfonic acid salts; organic acid salts such as fumaric acid salts, succinic acid salts, citric acid salts, tartaric acid salts, oxalic acid salts, maleic acid salts, acetic acid salts, malic acid salts, lactic acid salts, or ascorbic acid salts; and amino acid salts such as glycinate salts, phenylalanine salts, glutamic acid salts, or aspartic acid salts.

Production of Compounds

Compounds of formula (I) may be produced by reacting a hydrazine compound of formula (VI-1) or (VI-2) with a suitable carbonyl compound (compound C) in a suitable solvent, for example, toluene, in the presence of a suitable acid catalyst, for example, acetic acid.

wherein A, R⁵, R⁶, and R⁷ are as defined in formula (I).

The compound of formula (VI-1) and the compound of formula (VI-2) may be commercially available products, or alternatively may be produced by a production process which will be described later.

The compound of formula (VI-1) and the compound of formula (VI-2) may also be produced by reacting an amino compound of formula (VII) (compound A) with a suitable acid chloride (compound B), or by reacting an amino compound of formula (VII) (compound A) with a suitable carboxylic acid (compound B) in the presence of a suitable condensing agent, for example, 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride, to give an amide compound of formula (VIII), then adding hydrazine to the amide compound of formula (VIII) in a suitable solvent, for example, ethanol, and heating the mixture. A reduced form of formula (VI-2) can be produced by carrying out the hydrazination at a higher temperature and prolonging the reaction time. For example, the compound of formula (VI-1) can be produced under reaction conditions of 30 to 40° C. and 12 to 24 hr, while the compound of formula (VI-2) can be produced under reaction conditions of 110 to 120° C. and 72 to 96 hr.

wherein A and R⁵ are as defined in formula (I); and R²¹ represents a hydrogen atom or a protective group of carboxyl.

The compound wherein R⁵ represents phenyl substituted by formula (IV) or formula (V) can be produced by reacting a compound of formula (VIIIa) with a compound of formula (IV′) or formula (V′) (compound B′) to give a compound of formula (VIIIb) and then subjecting the compound of formula (VIIIb) to reactions shown in scheme 1 and scheme 2.

wherein A and R⁵ are as defined in formula (I); Q, X1, and R¹³ are as defined in formula (IV); X2, X3, R¹⁴ and R¹⁵ are as defined in formula (V); R²¹ represents a hydrogen atom or a protective group of carboxyl; Alk represents an alkylene chain having 1 to 6 carbon atoms; and Hal represents a halogen atom.

Tandem-type compounds of formula (I-3) can also be produced according to scheme 3. Specifically, a compound to which a compound of formula (VIIIa) has been bonded in a tandem manner can be produced by reacting the compound of formula (VIIIa) with H—NR²⁰⁵-T-NR^(205′)—H wherein R²⁰⁵, R^(205′), and T are as defined in formula (I-3), instead of the compound of formula (IV′) and the compound of formula (V′). The compound of formula (I-3) can be produced by subjecting this compound to reactions shown in scheme 1 and scheme 2.

An imine reduced form of formula (I) in which Z represents —NH—CR⁶R⁷R¹⁷ can be produced by dissolving the compound produced according to scheme 1 in a suitable solvent, for example, methanol, and reducing the compound with a suitable reducing agent, for example, sodium borohydride).

wherein A, R⁵, R⁶, R⁷, and R¹⁷ are as defined in formula (I).

Among amino compounds used as the starting compound in scheme 2, compounds in which ring A is a benzene ring can be synthesized by methods shown in schemes A to H.

wherein R²¹ represents a hydrogen atom or a protective group of carboxyl; Alk represents an alkylene chain having 2 to 7 carbon atoms; n is an integer of 1 to 6; Hal represents a halogen atom, preferably a bromine or chlorine atom; R³⁰¹, R³⁰², R³⁰³, R³⁰⁴, and R³⁰⁵ represent optionally substituted C₁₋₆ alkyl, optionally substituted C₂₋₆ alkenyl, optionally substituted aryl, or the like; R¹, R², R³, and R⁴ are as defined in formula (I).

In the above schemes, the esterification can be carried out by esterifying a commercially available carboxylic acid with a suitable esterifying agent, for example, 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride.

The introduction of the amino group can be carried out by allowing an alkylamino compound or an arylamino compound to act under basic condition, for example, potassium carbonate.

The reduction of the nitro group can be carried out using a suitable reducing agent, for example, palladium-carbon.

Use of Compounds

A group of sodium dependent phosphate transporters (NaPi) present in cells are known to be responsible for homeostasis of phosphorus in vivo. In particular, the phosphorus concentration of serum is generally regulated by phosphate absorption in intestinal epithelial cells and phosphate reabsorption in renal tubular cells, and the above phosphate transporters also participate in these mechanisms.

The compounds according to the present invention can inhibit these phosphate transporters that mainly specify phosphate absorption from the intestinal tract and phosphate reabsorption from the kidney (see Pharmacological Test Examples 1 to 3).

Further, the compounds according to the present invention can exhibit phosphate absorption inhibitory activity in the intestinal tract of rats (see Pharmacological Test Example 4).

Accordingly, the compounds according to the present invention can be used for the prevention or treatment of diseases for which serum phosphate lowering action is therapeutically effective.

The term “serum phosphate lowering action” as used herein means action that lowers phosphate concentration of serum. The phosphate concentration of serum is specified by (i) absorption from the intestinal tract and excretion into urine and feces and (ii) introduction and discharge with respect to cells in vivo and calcified tissue typified by osseous tissues. The “serum phosphate lowering action” as used herein embraces the action of lowering of the serum phosphate concentration in the case of action on a healthy living body and is not always limited to the action of lowering of serum phosphate concentration in hyperphosphatemia.

Further, the compounds according to the present invention can be used for the prevention or treatment of diseases for which phosphate transport inhibition is therapeutically effective.

The term “phosphate transport inhibition” as used herein means the inhibition of transport activity of phosphate transporters present on cell membranes of object cells. Object cells include epithelial cells of small intestine, renal epithelial cells, pulmonary epithelial cells, vascular endothelial cells, vascular smooth muscle cells, or osteoblasts.

Diseases for which the serum phosphate lowering action is effective therapeutically and diseases for which phosphate transport inhibition is therapeutically effective include (1) hyperphosphatemia, (2) renal failure and chronic renal failure, (3) secondary hyperparathyroidism and diseases related thereto, (4) metabolic osteopathy, (5) diseases for which the suppression of calcium and/or phosphorus product is effective therapeutically, and (6) other hyperphosphatemia-related diseases.

(1) Hyperphosphatemia

The compounds according to the present invention can lower the phosphate concentration of serum and can inhibit phosphate transport and thus can be used for the prevention or treatment of hyperphosphatemia. The term “hyperphosphatemia” as used herein means such a state that the phosphate concentration of serum is beyond a clinically defined normal region.

(2) Renal Failure and Chronic Renal Failure

Regarding renal failure and chronic renal failure, it has recently been suggested that an increase in serum phosphate concentration per se is an exacerbation factor of renal failure. In fact, there are a series of reports on that the progress of the renal failure can be delayed by restriction of phosphate ingestion in chronic renal failure patients (Maschio et al., Kidney Int., 22:371-376, 1982, Maschio et al., Kidney Int., 24:S273-277, 1983, Barsotti et al., Kidney Int. 24:S278-284, 1983).

Accordingly, the compounds according to the present invention which can inhibit phosphate transport and can lower phosphate concentration of serum can be used for the prevention or treatment of the renal failure and the chronic renal failure.

(3) Secondary Hyperparathyroidism and Primary Hyperparathyroidism and Diseases Related Thereto

It is known that hyperphosphatemia secondarily leads to hypocalcemia and thus induces secondary hyperparathyroidism. Accordingly, the compounds according to the present invention can be used for the prevention and treatment of secondary hyperparathyroidism.

Further, in recent years, there are a report that a rise of phosphate concentration promotes the secretion of PTH (parathyroid hormone) from parathyroid cells (Almanden Y et al., J Bone Miner Res 11:970-976, 1996), a report that phosphorus restriction suppresses the secretion (Rachel K et al., J Clin Invest 96.327-333, 1995), a report that hyperplasia of parathyroids is suppressed (Slatopolsky E et al., J Clin Invest 97:2534-2540, 1996) and the like. When these reports suggesting that the serum phosphate concentration per se participates in hyperplasia of parathyroids and PTH secretion are taken into consideration, it can be said that the compounds according to the present invention can be used for the prevention and treatment of secondary hyperparathyroidism as well as primary hyperparathyroidism through a lowering in serum phosphate concentration. Further, the compounds according to the present invention can be used for the prevention and treatment of renal osteodystrophy induced by secondary hyperparathyroidism, that is, osteitis fibrosa, ostealgia and arthralgia, bone deformity, fracture and the like.

The compounds according to the present invention can prevent and treat secondary hyperparathyroidism and thus can also be used for the prevention and treatment of diseases said to be induced by PTH increase in the secondary hyperparathyroidism, for example, central or peripheral nervous system damage, anemia, myocardiopathy, hyperlipidemia, anomaly of saccharometabolism, pruritus cutaneus, tendon rupture, sexual dysfunction, muscle damage, skin ischemic ulcer, growth retardation, heart conduction disturbance, pulmonary diffusing impairment, immune deficiency, ostealgia and arthralgia, bone deformity, or fracture.

(4) Calcium and Phosphorus Metabolic Disorder

The compounds according to the present invention can remedy clinical conditions of phosphorus metabolic disorder and, at the same time, are considered to have the effect of remedying clinical conditions of metabolic disorder of minerals including calcium. Accordingly, the compounds according to the present invention can be used for the prevention and treatment of calcium and phosphorus metabolic disorders such as metabolic osteopathy.

(5) Diseases for which Suppression of Calcium and/or Phosphorus Product is Therapeutically Effective

In dialysis patients, when poor control of serum phosphate concentration due to administration of a large amount of calcium preparations and administration of a large amount of vitamin D, and overconsumption of proteins is likely to cause ectopic calcification as a result of a rise of calcium and phosphorus product in blood and is in its turn causative of circulatory disorders derived from calcification of blood circulatory systems including coronary artery (Braun J et al., Am J Kidney Dis. 27:394-401, 1996, Goodman W G et al., N Engl J Med 342:1478-1483, 2000, Kimura K et al., Kidney Int. 71: S238-241, 1999). In this case, downward revision of calcium and phosphorus product is effective in remedying clinical condition (Geoffrey A B et al., Am J Kidney Dis. 31:607-617, 1998). The compounds according to the present invention are hyperphosphatemia improving drugs different from calcium preparations and thus can lower the phosphate concentration of serum without a rise of calcium concentration of serum. Thus, the compounds according to the present invention can be used for the treatment of diseases for which the suppression of calcium and/or phosphorus product in blood vessels is therapeutically effective. Such diseases include calcification of cardiovascular system in dialysis patients, age-related arterial sclerosis, diabetic vasculopathy, calcification of soft tissue, metastatic calcification, and ectopic calcification. Since a rise of calcium and phosphorus product is recognized as a risk factor of clinical conditions of red eye, arthralgia, myalgia, pruritus cutaneus, heart conduction disturbance, pulmonary diffusing impairment, angina pectoris, cardiac infarction, or heart failure induced by cardiac murmur or valvular disease (Tetsuo Tagami, Jin To Toseki (Kidney and Dialysis), Vol. 49:189-191, 2000), the compounds according to the present invention can also be used for the prevention and treatment of these diseases.

(6) Other Diseases Related to Hyperphosphatemia

In addition to the above diseases (1) to (5), hypoparathyroidism, pseudohypoparathyroidism, hypocalcemia, hypercalciuria, vitamin D toxicosis, acromegaly, overdose of phosphate, acidosis, state of hypercatabolism, rhabdomyolysis, hemolytic anemia, climacteric disturbance, malignant tumor, tumor lysis syndrome, and tumoral calcinosis involve hyperphosphatemia. Therefore, the compounds according to the present invention can also be used for the prevention and treatment of these diseases.

According to the present invention, there is provided a serum phosphate concentration lowering agent comprising the compound according to the present invention.

According to the present invention, there is provided a phosphate transport inhibitor comprising the compound according to the present invention.

According to the present invention, there is provided a method for lowering serum phosphate concentration, comprising administering the compound according to the present invention to a human or a mammal other than a human.

According to the present invention, there is provided a method for inhibiting phosphate transport, comprising administering the compound according to the present invention to a human or mammal other than a human.

Pharmaceutical Preparation

The compounds according to the present invention can be administered to human and non-human animals orally or parenterally by administration routes, for example, intraoral, nasal administration, transpulmonary administration, intrarectal administration, percutaneous administration, subcutaneous administration, or intravenous administration. Therefore, the compounds according to the present invention can be formulated into suitable dosage forms according to the administration routes. Dosage forms suitable for the above administration routes include tablets, capsules, granules, powders, ointments, poultices, aerosols, suppositories, and injections.

The compound according to the present invention per se can be administered to patients, or alternatively may be administered together with general-purpose preparation additives to patients.

The pharmaceutical composition according to the present invention can be produced according to a well-known formulation technique by using the compound according to the present invention together with the following additives.

For example, oral preparations, that is, tablets, capsules, granules, and powders, can be produced by conventional methods with the compounds according to the present invention and suitable preparation additives. Additives usable for oral preparations include excipients, binders, disintegrants, and lubricants. They may be used either solely or in a combination of two or more. Excipients include, for example, lactose, mannitol, corn starch, and calcium carbonate. Binders include, for example, gum arabic, tragacanth, gelatin, and methylcellulose. Disintegrants include, for example, corn starch, crystalline cellulose, and carboxymethylcellulose sodium. Lubricants include, for example, talc, and magnesium stearate.

Oral preparations containing the compound according to the present invention may be coated with a coating agent according to a well known method. Coating agents usable herein include, for example, hydroxypropylcellulose, hydroxypropylmethylcellulose, aminoalkylmethacrylate copolymer, hydroxypropylmethylcellulose phthalate, and carboxymethylethylcellulose.

Oral preparations can be modified for effectively drawing phosphate absorption inhibition from intestinal tracts of the compound according to the present invention.

When the compounds according to the present invention are orally administered, there is a possibility that, after the inhibition of phosphate transport carriers in small intestine epithelial cells, they are absorbed in the body and inhibit phosphate transport carriers in vascular endothelial cells, pulmonary epithelial cells, renal epithelial cells, osteoblasts and the like. Accordingly, the compounds according to the present invention have the possibility of inhibiting phosphate absorption from the intestine and further inhibiting phosphate absorption in the kidney to synergistically and effectively lower the phosphate concentration of serum. However, the possibility of exhibiting unknown toxicity upon absorption of the compounds according to the present invention in the body cannot be denied. To avoid this phenomenon, a technique may be adopted in which the compounds according to the present invention can specifically inhibit only small intestine epithelium, which is the first barrier for phosphate absorption from outside of the body, without the absorption from the intestinal tract. For example, the absorption of the compound per se from the intestinal tract can be prevented by bonding an inert water-soluble polymer to the compounds according to the present invention to increase the water solubility and molecular weight. Water soluble polymers usable herein include, for example, polyethylene glycol, dextran, and gelatin.

An enteric coating may be applied to the oral preparation according to the present invention for specific dissolution in the intestinal tract after oral administration. The enteric coating may be carried out by a well-known method using an enteric coating agent. Enteric coating agents include, for example, hydroxypropylmethylcellulose phthalate, hydroxypropylmethylcellulose acetate succinate, carboxymethylethylcellulose, and methacrylic acid copolymers.

Further, any foamable substance, which, after oral administration, can promote dissolution speed of the preparation in the intestinal tract to enhance the concentration of the effective ingredient, can be added to the oral preparation according to the present invention. Substances which are foamable upon dissolution include, for example, a combination of sodium hydrogencarbonate and citric acid.

Further, any substance, which, after oral administration, can improve the residence of the preparation in the intestinal tract, can be added to the oral preparation according to the present invention. Substances which can improve the residence include substances which become viscous upon dissolution, and examples thereof include sodium alginate, carboxymethylcellulose sodium, hydroxyethylcellulose, hydroxypropylcellulose, hydroxypropylmethylcellulose, polyvinyl alcohol, polyvinyl pyrrolidone, carboxylvinyl polymer, and chitosan.

In the oral preparation according to the present invention, the above modification methods may be properly used in combination.

The compounds according to the present invention and suitable preparation additives may be used for the manufacture of injections by a general-purpose method. Additives usable in injections include diluents, pH adjustors, tonicity adjusting agents, dissolution aids, and preservatives. They may be used either solely or in a combination of two or more. Diluents include, for example, distilled water for injections. pH adjustors include, for example, hydrochloric acid, sodium hydroxide, a combination of acetic acid with sodium acetate, and a combination of disodium hydrogenphosphate with sodium dihydrogenphosphate. Tonicity adjusting agents include, for example, sodium chloride, glucose, mannitol, and glycine. Dissolution aids include, for example, ethanol, Polysorbate 20, Polysorbate 80, sucrose fatty acid ester, and propylene glycol. Preservatives include, for example, chlorobutanol, benzalconium chloride, and benzethonium chloride.

For the compounds according to the present invention, the dose may be appropriately determined in consideration of particular conditions, for example, the age, weight, sex, type of disease, and severity of condition of patients, and the preparation may be administered, for example, in an amount of 0.1 to 1000 mg/kg, preferably 0.5 to 100 mg/kg, more preferably 1 to 20 mg/kg. This dose may be administered at a time daily or divided doses of several times daily.

EXAMPLES

The present invention is further illustrated by the following Examples that are not intended as a limitation of the scope of the invention.

Example 1 Compound 1 3,4-Dimethoxy-N-[2-(3-phenyl-allylidene-hydrazinocarbonyl)-phenyl]-benzamide

Methyl 2-aminobenzoate (compound A) (2.0 g) was dissolved in anhydrous methylene chloride (40.0 ml). Subsequently, pyridine (2.0 ml) and 3,4-dimethoxybenzoyl chloride (compound B) (3.14 g) were added to the solution at room temperature, and the mixture was stirred at that temperature for 30 min. After the completion of the reaction, distilled water was added thereto, and the mixture was subjected to separatory extraction with chloroform. The organic layer was washed with a saturated aqueous sodium chloride solution, was dried over sodium sulfate, and was then concentrated to give methyl 2-[(3,4-dimethoxybenzoyl)amino]benzoate as a useful intermediate (4.17 g, yield 100%).

Methyl 2-[(3,4-dimethoxybenzoyl)amino]benzoate (4.17 g) produced by the above reaction was dissolved in ethanol (40.0 ml). Hydrazine monohydrate (20.0 ml) was added at room temperature, and the mixture was stirred with heating under reflux for 12 hr. After the completion of the reaction, the reaction solution was allowed to cool at room temperature and was cooled under ice cooling to precipitate crystals. The precipitated crystals were collected by filtration through Kiriyama Rohto (40 mmφ) and were washed with ether to give N-(2-hydrazinocarbonyl-phenyl)-3,4-dimethoxybenzamide as a hydrazine compound (3.55 g, yield 91.3%).

N-(2-Hydrazinocarbonyl-phenyl)-3,4-dimethoxybenzamide (50.0 mg) was dissolved in anhydrous toluene (1.0 ml). Subsequently, a catalytic amount of acetic acid and trans-cinnamaldehyde (compound C) (40.0 μl) were added at room temperature, and the mixture was stirred with heating under reflux for 30 min. After the completion of the reaction, the reaction solution was allowed to cool at room temperature and was cooled under ice cooling to precipitate crystals. The precipitated crystals were filtered through Kiriyama Rohto (21 mmφ) and were washed with toluene and hexane. The crystals were dried through a vacuum pump to give the title compound 1 (39.0 mg, yield 57.0%).

Mass spectrometric value (ESI-MS) 428 (M−1)

Compound 2 N-[2-(2-Fluoro-benzylidene-hydrazinocarbonyl)-phenyl]-3,4-dimethoxy-benzamide

The title compound 2 was produced in the same manner as in Example 1.

Mass spectrometric value (ESI-MS) 420 (M−1)

Compound 3 3,4-Dimethoxy-N-[2-(2-methyl-benzylidene-hydrazinocarbonyl)-phenyl]-benzamide

The title compound 3 was produced in the same manner as in Example 1.

Mass spectrometric value (ESI-MS) 416 (M−1)

Compound 4 3,4-Dimethoxy-N-[2-(2-methoxy-benzylidene-hydrazinocarbonyl)-phenyl]-benzamide

The title compound 4 was produced in the same manner as in Example 1.

Mass spectrometric value (ESI-MS) 432 (M−1)

Compound 5 3,4-Dimethoxy-N-[2-(3-methoxy-benzylidene-hydrazinocarbonyl)-phenyl]-benzamide

The title compound 5 was produced in the same manner as in Example 1.

Mass spectrometric value (ESI-MS) 432 (M−1)

Compound 6 N-[2-(3,5-Di-tert-butyl-4-hydroxy-benzylidene-hydrazinocarbonyl)-phenyl]-3,4-dimethoxy-benzamide

The title compound 6 was produced in the same manner as in Example 1.

Mass spectrometric value (ESI-MS) 530 (M−1)

Compound 7 3,4-Dimethoxy-N-[2-(2-methyl-3-phenyl-allylidene-hydrazinocarbonyl)-phenyl]-benzamide

The title compound 7 was produced in the same manner as in Example 1.

Mass spectrometric value (ESI-MS) 442 (M−1)

Compound 8 N-[2-(3,5-Bis-trifluoromethyl-benzylidene-hydrazinocarbonyl)-phenyl]-3,4-dimethoxy-benzamide

The title compound 8 was produced in the same manner as in Example 1.

Mass spectrometric value (ESI-MS) 538 (M−1)

Compound 9 N-[2-(3-Cyano-benzylidene-hydrazinocarbonyl)-phenyl]-3,4-dimethoxy-benzamide

The title compound 9 was produced in the same manner as in Example 1.

Mass spectrometric value (ESI-MS) 427 (M−1)

Compound 10 N-[2-(2-Bromo-benzylidene-hydrazinocarbonyl)-phenyl]-3,4-dimethoxy-benzamide

The title compound 10 was produced in the same manner as in Example 1.

Mass spectrometric value (ESI-MS) 480 (M−1)

Compound 11 N-[2-(4-Hydroxy-3-methoxy-benzylidene-hydrazinocarbonyl)-phenyl]-3,4-dimethoxy-benzamide

The title compound 11 was produced in the same manner as in Example 1.

Mass spectrometric value (ESI-MS) 448 (M−1)

Compound 12 3,4-Dimethoxy-N-[2-(3,4,5-trimethoxy-benzylidene-hydrazinocarbonyl)-phenyl]-benzamide

The title compound 12 was produced in the same manner as in Example 1.

Mass spectrometric value (ESI-MS) 492 (M−1)

Compound 13 N-[4-Bromo-2-(3-phenyl-allylidene-hydrazinocarbonyl)-phenyl]-3,4-dimethoxy-benzamide

The title compound 13 was produced in the same manner as in Example 1.

Mass spectrometric value (ESI-MS) 508 (M−1)

Compound 14 N-[4-Bromo-2-(2-bromo-benzylidene-hydrazinocarbonyl)-phenyl]-3,4-dimethoxy-benzamide

The title compound 14 was produced in the same manner as in Example 1.

Mass spectrometric value (ESI-MS) 560 (M−1)

Compound 15 N-[2-(3-Fluoro-benzylidene-hydrazinocarbonyl)-phenyl]-3,4-dimethoxy-benzamide

The title compound 15 was produced in the same manner as in Example 1.

Mass spectrometric value (ESI-MS) 420 (M−1)

Compound 16 N-[2-(4-Fluoro-benzylidene-hydrazinocarbonyl)-phenyl]-3,4-dimethoxy-benzamide

The title compound 16 was produced in the same manner as in Example 1.

Mass spectrometric value (ESI-MS) 420 (M−1)

Compound 17 N-[2-(Benzylidene-hydrazinocarbonyl)-phenyl]-3,4-dimethoxy-benzamide

The title compound 17 was produced in the same manner as in Example 1.

Mass spectrometric value (ESI-MS) 402 (M−1)

Compound 18 N-[2-(3-Hydroxy-benzylidene-hydrazinocarbonyl)-phenyl]-3,4-dimethoxy-benzamide

The title compound 18 was produced in the same manner as in Example 1.

Mass spectrometric value (ESI-MS) 418 (M−1)

Compound 19 N-[2-(4-Hydroxy-benzylidene-hydrazinocarbonyl)-phenyl]-3,4-dimethoxy-benzamide

The title compound 19 was produced in the same manner as in Example 1.

Mass spectrometric value (ESI-MS) 418 (M−1)

Compound 20 3,4-Dimethoxy-N-[2-(3-methyl-benzylidene-hydrazinocarbonyl)-phenyl]-benzamide

The title compound 20 was produced in the same manner as in Example 1.

Mass spectrometric value (ESI-MS) 416 (M−1)

Compound 21 N-[2-(Furan-2-ylmethylene-hydrazinocarbonyl)-phenyl]-3,4-dimethoxy-benzamide

The title compound 21 was produced in the same manner as in Example 1.

Mass spectrometric value (ESI-MS) 392 (M−1)

Compound 22 3,4-Dimethoxy-N-[2-(5-methyl-furan-2-ylmethylene-hydrazinocarbonyl)-phenyl]-benzamide

The title compound 22 was produced in the same manner as in Example 1.

Mass spectrometric value (ESI-MS) 406 (M−1)

Compound 23 3,4-Dimethoxy-N-[2-(thiophen-2-ylmethylene-hydrazinocarbonyl)-phenyl]-benzamide

The title compound 23 was produced in the same manner as in Example 1.

Mass spectrometric value (ESI-MS) 408 (M−1)

Compound 24 3,4-Dimethoxy-N-[2-(thiophen-3-ylmethylene-hydrazinocarbonyl)-phenyl]-benzamide

The title compound 24 was produced in the same manner as in Example 1.

Mass spectrometric value (ESI-MS) 408 (M−1)

Compound 25 N-[2-(2,4-Dihydroxy-benzylidene-hydrazinocarbonyl)-phenyl]-3,4-dimethoxy-benzamide

The title compound 25 was produced in the same manner as in Example 1.

Mass spectrometric value (ESI-MS) 434 (M−1)

Compound 26 N-[2-(3,4-Dihydroxy-benzylidene-hydrazinocarbonyl)-phenyl]-3,4-dimethoxy-benzamide

The title compound 26 was produced in the same manner as in Example 1.

Mass spectrometric value (ESI-MS) 434 (M−1)

Compound 27 N-[2-(Benzylidene-hydrazinocarbonyl)-phenyl]-2-fluoro-benzamide

The title compound 27 was produced in the same manner as in Example 1.

Mass spectrometric value (ESI-MS) 360 (M−1)

Compound 28 N-[4-Bromo-2-(2-fluoro-benzylidene-hydrazinocarbonyl)-phenyl]-3,4-dimethoxy-benzamide

The title compound 28 was produced in the same manner as in Example 1.

Mass spectrometric value (ESI-MS) 500 (M−1)

Compound 29 N-[4-Bromo-2-(3-fluoro-benzylidene-hydrazinocarbonyl)-phenyl]-3,4-dimethoxy-benzamide

The title compound 29 was produced in the same manner as in Example 1.

¹H-NMR (CDCl₃, 400 MHz): δ 8.55 (1H, d, J=9.0 Hz), 8.32 (1H, bs), 7.49-7.67 (6H, m), 7.40 (1H, q, J=4.56 Hz), 7.13 (1H, q, J=5.53 Hz), 6.93 (1H, d, J=8.8 Hz), 3.98 (3H, s), 3.94 (3H, s)

Mass spectrometric value (ESI-MS) 500 (M−1)

Compound 30 N-[4-Bromo-2-(2-methyl-benzylidene-hydrazinocarbonyl)-phenyl]-3,4-dimethoxy-benzamide

The title compound 30 was produced in the same manner as in Example 1.

Mass spectrometric value (ESI-MS) 494 (M−1)

Compound 31 N-[4-Bromo-2-(3-methyl-benzylidene-hydrazinocarbonyl)-phenyl]-3,4-dimethoxy-benzamide

The title compound 31 was produced in the same manner as in Example 1.

Mass spectrometric value (ESI-MS) 494 (M−1)

Compound 32 N-[2-(3-Chloro-4-fluoro-benzylidene-hydrazinocarbonyl)-phenyl]-3,4-dimethoxy-benzamide

The title compound 32 was produced in the same manner as in Example 1.

Mass spectrometric value (ESI-MS) 454 (M−1)

Compound 33 3,4-Dimethoxy-N-[2-(4-trifluoromethoxy-benzylidene-hydrazinocarbonyl)-phenyl]-benzamide

The title compound 33 was produced in the same manner as in Example 1.

Mass spectrometric value (ESI-MS) 486 (M−1)

Compound 34 N-[2-(3-Bromo-4-methoxy-benzylidene-hydrazinocarbonyl)-phenyl]-3,4-dimethoxy-benzamide

The title compound 34 was produced in the same manner as in Example 1.

Mass spectrometric value (ESI-MS) 512 (M−1)

Compound 35 N-[2-(3-Chloro-benzylidene-hydrazinocarbonyl)-phenyl]-3,4-dimethoxy-benzamide

The title compound 35 was produced in the same manner as in Example 1.

Mass spectrometric value (ESI-MS) 436 (M−1)

Compound 36 N-[2-(4-Hydroxy-3,5-dimethyl-benzylidene-hydrazinocarbonyl)-phenyl]-3,4-dimethoxy-benzamide

The title compound 36 was produced in the same manner as in Example 1.

Mass spectrometric value (ESI-MS) 446 (M−1)

Compound 37 N-[2-(3-Ethoxy-4-hydroxy-benzylidene-hydrazinocarbonyl)-phenyl]-3,4-dimethoxy-benzamide

The title compound 37 was produced in the same manner as in Example 1.

Mass spectrometric value (ESI-MS) 462 (M−1)

Compound 38 2-Fluoro-N-[2-(4-fluoro-benzylidene-hydrazinocarbonyl)-phenyl]-benzamide

The title compound 38 was produced in the same manner as in Example 1.

Mass spectrometric value (ESI-MS) 378 (M−1)

Compound 39 2-Fluoro-N-[2-(3-hydroxy-benzylidene-hydrazinocarbonyl)-phenyl]-benzamide

The title compound 39 was produced in the same manner as in Example 1.

Mass spectrometric value (ESI-MS) 376 (M−1)

Compound 40 2-Fluoro-N-[2-(4-methyl-benzylidene-hydrazinocarbonyl)-phenyl]-benzamide

The title compound 40 was produced in the same manner as in Example 1.

Mass spectrometric value (ESI-MS) 374 (M−1)

Compound 41 N-[2-(4-Chloro-3-trifluoromethyl-benzylidene-hydrazinocarbonyl)-phenyl]-3,4-dimethoxy-benzamide

The title compound 41 was produced in the same manner as in Example 1.

Mass spectrometric value (ESI-MS) 504 (M−1)

Compound 42 N-[2-(4-Hydroxy-3-methyl-benzylidene-hydrazinocarbonyl)-phenyl]-3,4-dimethoxy-benzamide

The title compound 42 was produced in the same manner as in Example 1.

Mass spectrometric value (ESI-MS) 432 (M−1)

Compound 43 N-[2-(2,5-Dimethyl-benzylidene-hydrazinocarbonyl)-phenyl]-3,4-dimethoxy-benzamide

The title compound 43 was produced in the same manner as in Example 1.

Mass spectrometric value (ESI-MS) 430 (M−1)

Compound 44 N-[2-(2-Fluoro-5-trifluoromethyl-benzylidene-hydrazinocarbonyl)-phenyl]-3,4-dimethoxy-benzamide

The title compound 44 was produced in the same manner as in Example 1.

Mass spectrometric value (ESI-MS) 488 (M−1)

Compound 45 2-Fluoro-N-[2-(4-hydroxy-3-methyl-benzylidene-hydrazinocarbonyl)-phenyl]-benzamide

The title compound 45 was produced in the same manner as in Example 1.

Mass spectrometric value (ESI-MS) 390 (M−1)

Compound 46 N-[2-(2,5-Dimethyl-benzylidene-hydrazinocarbonyl)-phenyl]-2-fluoro-benzamide

The title compound 46 was produced in the same manner as in Example 1.

Mass spectrometric value (ESI-MS) 388 (M−1)

Compound 47 N-[2-(3-Fluoro-benzylidene-hydrazinocarbonyl)-phenyl]-4-methoxy-benzamide

The title compound 47 was produced in the same manner as in Example 1.

Mass spectrometric value (ESI-MS) 390 (M−1)

Compound 48 N-[2-(4-Fluoro-benzylidene-hydrazinocarbonyl)-phenyl]-4-methoxy-benzamide

The title compound 48 was produced in the same manner as in Example 1.

Mass spectrometric value (ESI-MS) 390 (M−1)

Compound 49 4-Methoxy-N-[2-(3-methyl-benzylidene-hydrazinocarbonyl)-phenyl]-benzamide

The title compound 49 was produced in the same manner as in Example 1.

Mass spectrometric value (ESI-MS) 386 (M−1)

Compound 50 N-[2-(3-Hydroxy-benzylidene-hydrazinocarbonyl)-phenyl]-4-methoxy-benzamide

The title compound 50 was produced in the same manner as in Example 1.

Mass spectrometric value (ESI-MS) 388 (M−1)

Compound 51 4-Methoxy-N-[2-(4-methyl-benzylidene-hydrazinocarbonyl)-phenyl]-benzamide

The title compound 51 was produced in the same manner as in Example 1.

Mass spectrometric value (ESI-MS) 386 (M−1)

Compound 52 N-[2-(4-Allyloxy-benzylidene-hydrazinocarbonyl)-phenyl]-3,4-dimethoxy-benzamide

The title compound 52 was produced in the same manner as in Example 1.

Mass spectrometric value (ESI-MS) 458 (M−1)

Compound 53 N-[2-(3,5-Dimethoxy-benzylidene-hydrazinocarbonyl)-phenyl]-3,4-dimethoxy-benzamide

The title compound 53 was produced in the same manner as in Example 1.

Mass spectrometric value (ESI-MS) 462 (M−1)

Compound 54 3,4-Dimethoxy-N-{2-[3-(3-trifluoromethyl-phenoxy)-benzylidene-hydrazinocarbonyl]-phenyl}-benzamide

The title compound 54 was produced in the same manner as in Example 1.

Mass spectrometric value (ESI-MS) 562 (M−1)

Compound 55 N-[2-(3-Fluoro-benzylidene-hydrazinocarbonyl)-phenyl]-3,5-dimethoxy-benzamide

The title compound 55 was produced in the same manner as in Example 1.

Mass spectrometric value (ESI-MS) 420 (M−1)

Compound 56 N-[2-(4-Fluoro-benzylidene-hydrazinocarbonyl)-phenyl]-3,5-dimethoxy-benzamide

The title compound 56 was produced in the same manner as in Example 1.

Mass spectrometric value (ESI-MS) 420 (M−1)

Compound 57 3,5-Dimethoxy-N-[2-(4-methyl-benzylidene-hydrazinocarbonyl)-phenyl]-benzamide

The title compound 57 was produced in the same manner as in Example 1.

Mass spectrometric value (ESI-MS) 416 (M−1)

Compound 58 N-[2-(3-Hydroxy-benzylidene-hydrazinocarbonyl)-phenyl]-3,5-dimethoxy-benzamide

The title compound 58 was produced in the same manner as in Example 1.

Mass spectrometric value (ESI-MS) 418 (M−1)

Compound 59 N-[4-Bromo-2-(3-chloro-benzylidene-hydrazinocarbonyl)-phenyl]-3,4-dimethoxy-benzamide

The title compound 59 was produced in the same manner as in Example 1.

Mass spectrometric value (ESI-MS) 516 (M−1)

Compound 60 N-[4-Bromo-2-(4-chloro-benzylidene-hydrazinocarbonyl)-phenyl]-3,4-dimethoxy-benzamide

The title compound 60 was produced in the same manner as in Example 1.

Mass spectrometric value (ESI-MS) 516 (M−1)

Compound 61 N-[4-Bromo-2-(4-fluoro-benzylidene-hydrazinocarbonyl)-phenyl]-3,4-dimethoxy-benzamide

The title compound 61 was produced in the same manner as in Example 1.

Mass spectrometric value (ESI-MS) 500 (M−1)

Compound 62 N-[4-Bromo-2-(4-methyl-benzylidene-hydrazinocarbonyl)-phenyl]-3,4-dimethoxy-benzamide

The title compound 62 was produced in the same manner as in Example 1.

Mass spectrometric value (ESI-MS) 494 (M−1)

Compound 63 N-[4-Bromo-2-(3-hydroxy-benzylidene-hydrazinocarbonyl)-phenyl]-3,4-dimethoxy-benzamide

The title compound 63 was produced in the same manner as in Example 1.

Mass spectrometric value (ESI-MS) 496 (M−1)

Compound 64 N-[4-Bromo-2-(4-hydroxy-benzylidene-hydrazinocarbonyl)-phenyl]-3,4-dimethoxy-benzamide

The title compound 64 was produced in the same manner as in Example 1.

Mass spectrometric value (ESI-MS) 496 (M−1)

Compound 65 N-[4-Chloro-2-(3-fluoro-benzylidene-hydrazinocarbonyl)-phenyl]-3,4-dimethoxy-benzamide

The title compound 65 was produced in the same manner as in Example 1.

Mass spectrometric value (ESI-MS) 454 (M−1)

Compound 66 N-[4-Chloro-2-(4-fluoro-benzylidene-hydrazinocarbonyl)-phenyl]-3,4-dimethoxy-benzamide

The title compound 66 was produced in the same manner as in Example 1.

Mass spectrometric value (ESI-MS) 454 (M−1)

Compound 67 N-[4-Chloro-2-(3-methyl-benzylidene-hydrazinocarbonyl)-phenyl]-3,4-dimethoxy-benzamide

The title compound 67 was produced in the same manner as in Example 1.

Mass spectrometric value (ESI-MS) 450 (M−1)

Compound 68 N-[4-Chloro-2-(4-methyl-benzylidene-hydrazinocarbonyl)-phenyl]-3,4-dimethoxy-benzamide

The title compound 68 was produced in the same manner as in Example 1.

¹H-NMR (CDCl₃, 400 MHz): δ 9.33 (1H, s), 8.72 (1H, d, J=8.76 Hz), 8.21 (1H, s), 7.48-7.68 (6H, m), 7.20-7.25 (1H, m), 6.92 (1H, d, J=8.56 Hz), 3.97 (3H, s), 3.93 (3H, s), 2.38 (3H, s)

Mass spectrometric value (ESI-MS) 450 (M−1)

Compound 69 N-[4-Chloro-2-(3-hydroxy-benzylidene-hydrazinocarbonyl)-phenyl]-3,4-dimethoxy-benzamide

The title compound 69 was produced in the same manner as in Example 1.

Mass spectrometric value (ESI-MS) 452 (M−1)

Compound 70 N-[4-Chloro-2-(4-hydroxy-benzylidene-hydrazinocarbonyl)-phenyl]-3,4-dimethoxy-benzamide

The title compound 70 was produced in the same manner as in Example 1.

Mass spectrometric value (ESI-MS) 452 (M−1)

Compound 71 N-[5-Chloro-2-(3-fluoro-benzylidene-hydrazinocarbonyl)-phenyl]-3,4-dimethoxy-benzamide

The title compound 71 was produced in the same manner as in Example 1.

Mass spectrometric value (ESI-MS) 454 (M−1)

Compound 72 N-[5-Chloro-2-(4-fluoro-benzylidene-hydrazinocarbonyl)-phenyl]-3,4-dimethoxy-benzamide

The title compound 72 was produced in the same manner as in Example 1.

Mass spectrometric value (ESI-MS) 454 (M−1)

Compound 73 N-[5-Chloro-2-(3-methyl-benzylidene-hydrazinocarbonyl)-phenyl]-3,4-dimethoxy-benzamide

The title compound 73 was produced in the same manner as in Example 1.

Mass spectrometric value (ESI-MS) 450 (M−1)

Compound 74 N-[5-Chloro-2-(4-methyl-benzylidene-hydrazinocarbonyl)-phenyl]-3,4-dimethoxy-benzamide

The title compound 74 was produced in the same manner as in Example 1.

Mass spectrometric value (ESI-MS) 452 (M−1)

Compound 75 N-[5-Chloro-2-(3-hydroxy-benzylidene-hydrazinocarbonyl)-phenyl]-3,4-dimethoxy-benzamide

The title compound 75 was produced in the same manner as in Example 1.

Mass spectrometric value (ESI-MS) 452 (M−1)

Compound 76 4-Fluoro-N-[2-(3-fluoro-benzylidene-hydrazinocarbonyl)-phenyl]-benzamide

The title compound 76 was produced in the same manner as in Example 1.

Mass spectrometric value (ESI-MS) 379 (M−1), 757 (2M−1)

Compound 77 4-Fluoro-N-[2-(4-fluoro-benzylidene-hydrazinocarbonyl)-phenyl]-benzamide

The title compound 77 was produced in the same manner as in Example 1.

Mass spectrometric value (ESI-MS) 378 (M−1)

Compound 78 4-Fluoro-N-[2-(3-methyl-benzylidene-hydrazinocarbonyl)-phenyl]-benzamide

The title compound 78 was produced in the same manner as in Example 1.

Mass spectrometric value (ESI-MS) 374 (M−1)

Compound 79 4-Fluoro-N-[2-(4-methyl-benzylidene-hydrazinocarbonyl)-phenyl]-benzamide

The title compound 79 was produced in the same manner as in Example 1.

Mass spectrometric value (ESI-MS) 374 (M−1)

Compound 80 4-Fluoro-N-[2-(3-hydroxy-benzylidene-hydrazinocarbonyl)-phenyl]-benzamide

The title compound 80 was produced in the same manner as in Example 1.

Mass spectrometric value (ESI-MS) 376 (M−1)

Compound 81 3-Fluoro-N-[2-(3-fluoro-benzylidene-hydrazinocarbonyl)-phenyl]-benzamide

The title compound 81 was produced in the same manner as in Example 1.

Mass spectrometric value (ESI-MS) 378 (M−1)

Compound 82 3-Fluoro-N-[2-(4-fluoro-benzylidene-hydrazinocarbonyl)-phenyl]-benzamide

The title compound 82 was produced in the same manner as in Example 1.

Mass spectrometric value (ESI-MS) 757 (2M−1)

Compound 83 3-Fluoro-N-[2-(3-methyl-benzylidene-hydrazinocarbonyl)-phenyl]-benzamide

The title compound 83 was produced in the same manner as in Example 1.

Mass spectrometric value (ESI-MS) 374 (M−1)

Compound 84 3-Fluoro-N-[2-(4-methyl-benzylidene-hydrazinocarbonyl)-phenyl]-benzamide

The title compound 84 was produced in the same manner as in Example 1.

Mass spectrometric value (ESI-MS) 374 (M−1)

Compound 85 3-Fluoro-N-[2-(3-hydroxy-benzylidene-hydrazinocarbonyl)-phenyl]-benzamide

The title compound 85 was produced in the same manner as in Example 1.

Mass spectrometric value (ESI-MS) 376 (M−1)

Compound 86 3-Fluoro-N-[2-(4-hydroxy-benzylidene-hydrazinocarbonyl)-phenyl]-benzamide

The title compound 86 was produced in the same manner as in Example 1.

Mass spectrometric value (ESI-MS) 376 (M−1)

Compound 87 N-[4-Bromo-2-(4-chloro-3-trifluoromethyl-benzylidene-hydrazinocarbonyl)-phenyl]-3,4-dimethoxy-benzamide

The title compound 87 was produced in the same manner as in Example 1.

Mass spectrometric value (ESI-MS) 582, 584 (M−1)

Compound 88 N-[4-Chloro-2-(4-chloro-3-trifluoromethyl-benzylidene-hydrazinocarbonyl)-phenyl]-3,4-dimethoxy-benzamide

The title compound 88 was produced in the same manner as in Example 1.

¹H-NMR (CDCl₃, 400 MHz): δ 8.49 (1H, d, J=8.08 Hz), 8.39 (1H, s), 8.06 (1H, s), 7.96 (1H, s), 7.49-7.60 (4H, m), 7.41 (1H, d, J=9.04 Hz), 6.94 (1H, d, J=8.56 Hz), 3.98 (3H, s,), 3.94 (3H, s)

Mass spectrometric value (ESI-MS) 538, 540 (M−1)

Compound 89 N-[2-(4-Chloro-3-trifluoromethyl-benzylidene-hydrazinocarbonyl)-phenyl]-3,5-dimethoxy-benzamide

The title compound 89 was produced in the same manner as in Example 1.

Mass spectrometric value (ESI-MS) 504, 506 (M−1)

Compound 90 N-[2-(4-Chloro-3-trifluoromethyl-benzylidene-hydrazinocarbonyl)-phenyl]-4-methoxy-benzamide

The title compound 90 was produced in the same manner as in Example 1.

Mass spectrometric value (ESI-MS) 474 (M−1)

Compound 91 N-[4-Bromo-2-(3,4-dimethyl-benzylidene-hydrazinocarbonyl)-phenyl]-3,4-dimethoxy-benzamide

The title compound 91 was produced in the same manner as in Example 1.

¹H-NMR (CDCl₃, 400 MHz): δ 9.53 (1H, s), 8.61 (1H, d, J=9.04 Hz), 8.21 (1H, s), 7.69 (1H, s), 7.59-7.62 (4H, m), 7.46-7.50 (1H, m), 7.17 (1H, d, J=7.56 Hz), 6.91 (1H, d, J=8.28 Hz), 3.97 (3H, s), 3.93 (3H, s), 2.28 (3H, s), 2.28 (3H, s)

Mass spectrometric value (ESI-MS) 508 (M−1)

Compound 92 N-[4-Chloro-2-(3,4-dimethyl-benzylidene-hydrazinocarbonyl)-phenyl]-3,4-dimethoxy-benzamide

The title compound 92 was produced in the same manner as in Example 1.

¹H-NMR (CDCl₃, 400 MHz): δ 9.60 (1H, s), 8.65 (1H, d, J=9.04 Hz), 8.21 (1H, s), 7.44-7.62 (6H, m), 7.17 (1H, d, J=7.80 Hz), 6.91 (1H, d, J=8.32 Hz), 3.97 (3H, s), 3.92 (3H, s), 2.28 (6H, s)

Mass spectrometric value (ESI-MS) 464 (M−1)

Compound 93 N-[2-(3,4-Dimethyl-benzylidene-hydrazinocarbonyl)-phenyl]-3,5-dimethoxy-benzamide

The title compound 93 was produced in the same manner as in Example 1.

Mass spectrometric value (ESI-MS) 430 (M−1)

Compound 94 N-[2-(3,4-Dimethyl-benzylidene-hydrazinocarbonyl)-phenyl]-4-methoxy-benzamide

The title compound 94 was produced in the same manner as in Example 1.

Mass spectrometric value (ESI-MS) 400 (M−1)

Compound 95 N-[2-(3,4-Dimethyl-benzylidene-hydrazinocarbonyl)-phenyl]-3-fluoro-benzamide

The title compound 95 was produced in the same manner as in Example 1.

Mass spectrometric value (ESI-MS) 388 (M−1)

Compound 96 N-[2-(3,4-Dimethyl-benzylidene-hydrazinocarbonyl)-phenyl]-4-fluoro-benzamide

The title compound 96 was produced in the same manner as in Example 1.

Mass spectrometric value (ESI-MS) 388 (M−1)

Compound 97 N-[4-Bromo-2-(3-bromo-4-methoxy-benzylidene-hydrazinocarbonyl)-phenyl]-3,4-dimethoxy-benzamide

The title compound 97 was produced in the same manner as in Example 1.

Mass spectrometric value (ESI-MS) 590 (M−1)

Compound 98 N-[2-(3-Bromo-4-methoxy-benzylidene-hydrazinocarbonyl)-4-chloro-phenyl]-3,4-dimethoxy-benzamide

The title compound 98 was produced in the same manner as in Example 1.

Mass spectrometric value (ESI-MS) 544 (M−1)

Compound 99 N-[2-(3-Bromo-4-methoxy-benzylidene-hydrazinocarbonyl)-phenyl]-3,5-dimethoxy-benzamide

The title compound 99 was produced in the same manner as in Example 1.

Mass spectrometric value (ESI-MS) 510 (M−1)

Compound 100 N-[2-(3-Bromo-4-methoxy-benzylidene-hydrazinocarbonyl)-phenyl]-4-methoxy-benzamide

The title compound 100 was produced in the same manner as in Example 1.

Mass spectrometric value (ESI-MS) 482 (M−1)

Compound 101 N-[2-(3-Bromo-4-methoxy-benzylidene-hydrazinocarbonyl)-phenyl]-3-fluoro-benzamide

The title compound 101 was produced in the same manner as in Example 1.

Mass spectrometric value (ESI-MS) 468, 470 (M−1)

Compound 102 N-[2-(3-Bromo-4-methoxy-benzylidene-hydrazinocarbonyl)-phenyl]-4-fluoro-benzamide

The title compound 102 was produced in the same manner as in Example 1.

Mass spectrometric value (ESI-MS) 468, 470 (M−1)

Compound 103 3,4-Dimethoxy-N-[2-(3-nitro-benzylidene-hydrazinocarbonyl)-phenyl]-benzamide

The title compound 103 was produced in the same manner as in Example 1.

Mass spectrometric value (ESI-MS) 447 (M−1)

Compound 104 N-[2-(4-Dimethylamino-benzylidene-hydrazinocarbonyl)-phenyl]-3,4-dimethoxy-benzamide

The title compound 104 was produced in the same manner as in Example 1.

Mass spectrometric value (ESI-MS) 445 (M−1)

Compound 105 N-[4-Bromo-2-(3-fluoro-benzylidene-hydrazinocarbonyl)-phenyl]-4-fluoro-benzamide

The title compound 105 was produced in the same manner as in Example 1.

Mass spectrometric value (ESI-MS) 458 (M−1)

Compound 106 N-[4-Bromo-2-(4-fluoro-benzylidene-hydrazinocarbonyl)-phenyl]-4-fluoro-benzamide

The title compound 106 was produced in the same manner as in Example 1.

Mass spectrometric value (ESI-MS) 456 (M−1)

Compound 107 N-[4-Bromo-2-(3-chloro-benzylidene-hydrazinocarbonyl)-phenyl]-4-fluoro-benzamide

The title compound 107 was produced in the same manner as in Example 1.

Mass spectrometric value (ESI-MS) 472, 474 (M−1)

Compound 108 N-[4-Bromo-2-(4-chloro-benzylidene-hydrazinocarbonyl)-phenyl]-4-fluoro-benzamide

The title compound 108 was produced in the same manner as in Example 1.

Mass spectrometric value (ESI-MS) 472, 474 (M−1)

Compound 109 N-[4-Bromo-2-(3-hydroxy-benzylidene-hydrazinocarbonyl)-phenyl]-4-fluoro-benzamide

The title compound 109 was produced in the same manner as in Example 1.

Mass spectrometric value (ESI-MS) 456, 458 (M−1)

Compound 110 N-[4-Bromo-2-(pyridin-3-ylmethylene-hydrazinocarbonyl)-phenyl]-3,4-dimethoxy-benzamide

The title compound 110 was produced in the same manner as in Example 1.

Mass spectrometric value (ESI-MS) 483 (M−1)

Compound 111 N-[4-Chloro-2-(pyridin-3-ylmethylene-hydrazinocarbonyl)-phenyl]-3,4-dimethoxy-benzamide

The title compound III was produced in the same manner as in Example 1.

Mass spectrometric value (ESI-MS) 437 (M−1)

Compound 112 4-Methoxy-N-[2-(pyridin-3-ylmethylene-hydrazinocarbonyl)-phenyl]-benzamide

The title compound 112 was produced in the same manner as in Example 1.

Mass spectrometric value (ESI-MS) 373 (M−1)

Compound 113 4-Fluoro-N-[2-(pyridin-3-ylmethylene-hydrazinocarbonyl)-phenyl]-benzamide

The title compound 113 was produced in the same manner as in Example 1.

Mass spectrometric value (ESI-MS) 361 (M−1)

Compound 114 N-[4-Bromo-2-(3-fluoro-benzylidene-hydrazinocarbonyl)-phenyl]-3,5-dimethoxy-benzamide

The title compound 114 was produced in the same manner as in Example 1.

Mass spectrometric value (ESI-MS) 498 (M−1)

Compound 115 N-[4-Bromo-2-(4-fluoro-benzylidene-hydrazinocarbonyl)-phenyl]-3,5-dimethoxy-benzamide

The title compound 115 was produced in the same manner as in Example 1.

Mass spectrometric value (ESI-MS) 498, 500 (M−1)

Compound 116 N-[4-Bromo-2-(3-chloro-benzylidene-hydrazinocarbonyl)-phenyl]-3,5-dimethoxy-benzamide

The title compound 116 was produced in the same manner as in Example 1.

Mass spectrometric value (ESI-MS) 516, 518 (M−1)

Compound 117 N-[4-Bromo-2-(4-chloro-benzylidene-hydrazinocarbonyl)-phenyl]-3,5-dimethoxy-benzamide

The title compound 117 was produced in the same manner as in Example 1.

Mass spectrometric value (ESI-MS) 514, 516 (M−1)

Compound 118 N-[4-Bromo-2-(3-methyl-benzylidene-hydrazinocarbonyl)-phenyl]-3,5-dimethoxy-benzamide

The title compound 118 was produced in the same manner as in Example 1.

Mass spectrometric value (ESI-MS) 496 (M−1)

Compound 119 N-[4-Bromo-2-(4-methyl-benzylidene-hydrazinocarbonyl)-phenyl]-3,5-dimethoxy-benzamide

The title compound 119 was produced in the same manner as in Example 1.

Mass spectrometric value (ESI-MS) 494 (M−1)

Compound 120 N-[2-(3-Fluoro-benzylidene-)-hydrazinocarbonyl)-phenyl)-3-trifluoromethoxy-benzamide

The title compound 120 was produced in the same manner as in Example 1.

Mass spectrometric value (ESI-MS) 444 (M−1)

Compound 121 N-[2-(4-Fluoro-benzylidene-)-hydrazinocarbonyl)-phenyl)-3-trifluoromethoxy-benzamide

The title compound 121 was produced in the same manner as in Example 1.

Mass spectrometric value (ESI-MS) 444 (M−1)

Compound 122 N-[2-(3-Chloro-benzylidene-)-hydrazinocarbonyl)-phenyl)-3-trifluoromethoxy-benzamide

The title compound 122 was produced in the same manner as in Example 1.

Mass spectrometric value (ESI-MS) 459, 461 (M−1)

Compound 123 N-[2-(4-Chloro-benzylidene-)-hydrazinocarbonyl)-phenyl)-3-trifluoromethoxy-benzamide

The title compound 123 was produced in the same manner as in Example 1.

Mass spectrometric value (ESI-MS) 459, 461 (M−1)

Compound 124 N-[2-(4-Methyl-benzylidene-)-hydrazinocarbonyl)-phenyl)-3-trifluoromethoxy-benzamide

The title compound 124 was produced in the same manner as in Example 1.

Mass spectrometric value (ESI-MS) 440 (M−1)

Compound 125 N-[4-(3-Dimethylamino-propoxy)-2-(4-fluoro-benzylidene-hydrazinocarbonyl)-phenyl]-3,4-dimethoxy-benzamide

The title compound 125 was produced in the same manner as in Example 2, except that N-(2-chloroethyl)-N,N-dimethylamine hydrochloride was changed to 3-dimethylaminopropyl chloride hydrochloride.

Mass spectrometric value (ESI-MS) 521, 523 (M−1)

Compound 126 N-[4-Chloro-2-(3,4-dimethoxy-benzylidene-hydrazinocarbonyl)-phenyl]-3,4-dimethoxy-benzamide

The title compound 126 was produced in the same manner as in Example 1.

Mass spectrometric value (ESI-MS) 496 (M−1)

Compound 127 N-[4-Bromo-2-(3,4-dimethoxy-benzylidene-hydrazinocarbonyl)-phenyl]-3,4-dimethoxy-benzamide

The title compound 127 was produced in the same manner as in Example 1.

Mass spectrometric value (ESI-MS) 540 (M−1)

Compound 128 N-[4-Bromo-2-(3,4-dimethoxy-benzylidene-hydrazinocarbonyl)-phenyl]-3,5-dimethoxy-benzamide

The title compound 128 was produced in the same manner as in Example 1.

Mass spectrometric value (ESI-MS) 542 (M−1)

Compound 129 N-[2-(3-Fluoro-benzylidene-hydrazinocarbonyl)-phenyl]-nicotinamide

The title compound 129 was produced in the same manner as in Example 1.

Mass spectrometric value (ESI-MS) 361 (M−1)

Compound 130 N-[2-(4-Fluoro-benzylidene-hydrazinocarbonyl)-phenyl]-nicotinamide

The title compound 130 was produced in the same manner as in Example 1.

¹H-NMR (CDCl₃, 400 MHz): δ 9.69 (1H, s), 9.28 (1H, s), 8.77 (1H, dd, J=1.44 Hz, J=4.88 Hz), 8.66 (1H, d, J=7.80 Hz), 8.25-8.33 (2H, m), 7.81 (2H, s), 7.50-7.60 (2H, m), 7.43 (1H, dd, J=4.88 Hz, J=8.04 Hz), 7.05-7.15 (3H, m)

Mass spectrometric value (ESI-MS) 361 (M−1)

Compound 131 N-[2-(3-Methyl-benzylidene-hydrazinocarbonyl)-phenyl]-nicotinamide

The title compound 131 was produced in the same manner as in Example 1.

Mass spectrometric value (ESI-MS) 357 (M−1)

Compound 132 N-[2-(4-Methyl-benzylidene-hydrazinocarbonyl)-phenyl]-nicotinamide

The title compound 132 was produced in the same manner as in Example 1.

Mass spectrometric value (ESI-MS) 357 (M−1)

Compound 133 N-[2-(3,4-Dimethyl-benzylidene-hydrazinocarbonyl)-phenyl]-nicotinamide

The title compound 133 was produced in the same manner as in Example 1.

Mass spectrometric value (ESI-MS) 371 (M−1)

Compound 134 N-[2-(3-Fluoro-benzylidene-hydrazinocarbonyl)-phenyl]-isonicotinamide

The title compound 134 was produced in the same manner as in Example 1.

Mass spectrometric value (ESI-MS) 361 (M−1)

Compound 135 N-[2-(4-Fluoro-benzylidene-hydrazinocarbonyl)-phenyl]-isonicotinamide

The title compound 135 was produced in the same manner as in Example 1.

Mass spectrometric value (ESI-MS) 361 (M−1)

Compound 136 N-[2-(3-Methyl-benzylidene-hydrazinocarbonyl)-phenyl]-isonicotinamide

The title compound 136 was produced in the same manner as in Example 1.

Mass spectrometric value (ESI-MS) 357 (M−1)

Compound 137 N-[2-(4-Methyl-benzylidene-hydrazinocarbonyl)-phenyl]-isonicotinamide

The title compound 137 was produced in the same manner as in Example 1.

Mass spectrometric value (ESI-MS) 357 (M−1)

Compound 138 N-[2-(3,4-Dimethyl-benzylidene-hydrazinocarbonyl)-phenyl]-isonicotinamide

The title compound 138 was produced in the same manner as in Example 1.

Mass spectrometric value (ESI-MS) 371 (M−1)

Example 2 Compound 139 N-[4-(2-Dimethylamino-ethoxy-)-2-(4-fluoro-benzylidene-hydrazinocarbonyl)-phenyl]-3,4-dimethoxy-benzamide

N-[2-(4-Fluoro-benzylidene-hydrazinocarbonyl)-4-hydroxy-phenyl]-3,4-dimethoxy-benzamide (50 mg) synthesized in the same manner as in Example 1 was dissolved in anhydrous DMF (1.5 ml). NaH (60% in oil, 20 mg) was added to the solution at room temperature, and the mixture was stirred at that temperature for 5 min. Subsequently, N-(2-chloroethyl)-N,N-dimethylamine hydrochloride (47 mg) was added to the reaction solution at room temperature, and the mixture was stirred at that temperature for 12 hr. After the completion of the reaction, distilled water was added dropwise thereto under ice cooling and the mixture was subjected to separatory extraction with ethyl acetate. The organic layer was washed with saturated brine and was dried over sodium sulfate, and the organic layer was concentrated under the reduced pressure. The residue was purified by preparative TLC to give the title compound 139 (32 mg, yield 57.1%).

Mass spectrometric value (ESI-MS) 507 (M−1)

Compound 140 N-[4-(2-Diethylamino-ethoxy)-2-(4-fluoro-benzylidene-hydrazinocarbonyl)-phenyl]-3,4-dimethoxy-benzamide

The title compound 140 was produced in the same manner as in Example 2, except that N-(2-chloroethyl)-N,N-dimethylamine hydrochloride was changed to 2-diethylaminoethyl chloride hydrochloride.

Mass spectrometric value (ESI-MS) 535 (M−1)

Compound 141 N-[2-(3-Fluoro-benzylidene-hydrazinocarbonyl)-4-methoxy-phenyl]-3,4-dimethoxy-benzamide

The title compound 141 was produced in the same manner as in Example 1.

Mass spectrometric value (ESI-MS) 450 (M−1)

Compound 142 N-[2-(4-Fluoro-benzylidene-hydrazinocarbonyl)-4-methoxy-phenyl]-3,4-dimethoxy-benzamide

The title compound 142 was produced in the same manner as in Example 1.

Mass spectrometric value (ESI-MS) 450 (M−1)

Compound 143 3,4-Dimethoxy-N-[4-methoxy-2-(3-methyl-benzylidene-hydrazinocarbonyl)-phenyl]-benzamide

The title compound 143 was produced in the same manner as in Example 1.

Mass spectrometric value (ESI-MS) 446 (M−1)

Compound 144 3,4-Dimethoxy-N-[4-methoxy-2-(4-methyl-benzylidene-hydrazinocarbonyl)-phenyl]-benzamide

The title compound 144 was produced in the same manner as in Example 1.

Mass spectrometric value (ESI-MS) 446 (M−1)

Compound 145 N-[2-(3,4-Dimethyl-benzylidene-hydrazinocarbonyl)-4-methoxy-phenyl]-3,4-dimethoxy-benzamide

The title compound 145 was produced in the same manner as in Example 1.

Mass spectrometric value (ESI-MS) 460 (M−1)

Compound 146 N-[2-(3-Fluoro-benzylidene-hydrazinocarbonyl)-4-methyl-phenyl]-3,4-dimethoxy-benzamide

The title compound 146 was produced in the same manner as in Example 1.

Mass spectrometric value (ESI-MS) 434 (M−1)

Compound 147 N-[2-(4-Fluoro-benzylidene-hydrazinocarbonyl)-4-methyl-phenyl]-3,4-dimethoxy-benzamide

The title compound 147 was produced in the same manner as in Example 1.

Mass spectrometric value (ESI-MS) 434 (M−1)

Compound 148 3,4-Dimethoxy-N-[4-methyl-2-(3-methyl-benzylidene-hydrazinocarbonyl)-phenyl]-benzamide

The title compound 148 was produced in the same manner as in Example 1.

Mass spectrometric value (ESI-MS) 430 (M−1)

Compound 149 3,4-Dimethoxy-N-[4-methyl-2-(4-methyl-benzylidene-hydrazinocarbonyl)-phenyl]-benzamide

The title compound 149 was produced in the same manner as in Example 1.

Mass spectrometric value (ESI-MS) 430 (M−1)

Compound 150 N-[2-(3,4-Dimethyl-benzylidene-hydrazinocarbonyl)-4-methyl-phenyl]-3,4-dimethoxy-benzamide

The title compound 150 was produced in the same manner as in Example 1.

Mass spectrometric value (ESI-MS) 444 (M−1)

Compound 151 Furan-2-carboxylic acid [4-bromo-2-(3-fluoro-benzylidene-hydrazinocarbonyl)-phenyl]-amide

The title compound 151 was produced in the same manner as in Example 1.

Mass spectrometric value (ESI-MS) 428 (M−1)

Compound 152 Furan-2-carboxylic acid [4-bromo-2-(4-fluoro-benzylidene-hydrazinocarbonyl)-phenyl]-amide

The title compound 152 was produced in the same manner as in Example 1.

Mass spectrometric value (ESI-MS) 428 (M−1)

Compound 153 Furan-2-carboxylic acid [4-bromo-2-(3-methyl-benzylidene-hydrazinocarbonyl)-phenyl]-amide

The title compound 153 was produced in the same manner as in Example 1.

Mass spectrometric value (ESI-MS) 426 (M−1)

Compound 154 Furan-2-carboxylic acid [4-bromo-2-(4-methyl-benzylidene-hydrazinocarbonyl)-phenyl]-amide

The title compound 154 was produced in the same manner as in Example 1.

Mass spectrometric value (ESI-MS) 424 (M−1)

Compound 155 Furan-2-carboxylic acid [4-bromo-2-(3,4-dimethyl-benzylidene-hydrazinocarbonyl)-phenyl]-amide

The title compound 155 was produced in the same manner as in Example 1.

Mass spectrometric value (ESI-MS) 438 (M−1)

Compound 156 Furan-2-carboxylic acid [4-bromo-2-(4-chloro-3-trifluoromethyl-benzylidene-hydrazinocarbonyl)-phenyl]-amide

The title compound 156 was produced in the same manner as in Example 1.

Mass spectrometric value (ESI-MS) 513, 514 (M−1)

Compound 157 Thiophene-2-carboxylic acid [4-bromo-2-(3-fluoro-benzylidene-hydrazinocarbonyl)-phenyl]-amide

The title compound 157 was produced in the same manner as in Example 1.

Mass spectrometric value (ESI-MS) 446 (M−1)

Compound 158 Thiophene-2-carboxylic acid [4-bromo-2-(4-fluoro-benzylidene-hydrazinocarbonyl)-phenyl]-amide

The title compound 158 was produced in the same manner as in Example 1.

Mass spectrometric value (ESI-MS) 446 (M−1)

Compound 159 Thiophene-2-carboxylic acid [4-bromo-2-(3-methyl-benzylidene-hydrazinocarbonyl)-phenyl]-amide

The title compound 159 was produced in the same manner as in Example 1.

Mass spectrometric value (ESI-MS) 440 (M−1)

Compound 160 Thiophene-2-carboxylic acid [4-bromo-2-(4-methyl-benzylidene-hydrazinocarbonyl)-phenyl]-amide

The title compound 160 was produced in the same manner as in Example 1.

Mass spectrometric value (ESI-MS) 440 (M−1)

Compound 161 Thiophene-2-carboxylic acid [4-bromo-2-(3,4-dimethyl-benzylidene-hydrazinocarbonyl)-phenyl]-amide

The title compound 161 was produced in the same manner as in Example 1.

Mass spectrometric value (ESI-MS) 454, 456 (M−1)

Compound 162 Thiophene-2-carboxylic acid [4-bromo-2-(4-chloro-3-trifluoromethyl-benzylidene-hydrazinocarbonyl)-phenyl]-amide

The title compound 162 was produced in the same manner as in Example 1.

Mass spectrometric value (ESI-MS) 530 (M−1)

Example 3 Compound 163 N-[2-(3,4-Dimethyl-benzylidene-hydrazinocarbonyl)-phenyl]-isonicotinamide hydrochloride

A 10% hydrochloric acid-methanol solution (1.0 ml) was added to compound 138 (50 mg) synthesized in the same manner as in Example 1 at room temperature. Further, diethyl ether (5.0 ml) was added thereto, and the mixture was stirred for 30 sec. The reaction solution as such was filtered through Kiriyama Rohto (21 mmφ), and the crystals were washed with diethyl ether to give the title compound 163 (47 mg, yield 85.6%).

¹H-NMR (MeOH-d₄, 400 MHz): δ 8.97 (2H, d, J=6.84 Hz), 8.49 (1H, d, J=8.08 Hz), 8.41 (2H, d, J=6.56 Hz), 8.23 (1H, s), 7.84 (1H, d, J=6.56 Hz), 7.56-7.61 (2H, m), 7.44 (1H, d, J=7.80 Hz), 7.28 (1H, dd, J=7.32 Hz, J=7.32 Hz), 7.12 (1H, d, J=7.80 Hz), 2.23 (3H, s), 2.22 (3H, s)

Mass spectrometric value (ESI-MS) 371 (M−1)

Compound 164 N-[2-(4-Methyl-benzylidene-hydrazinocarbonyl)-phenyl]-nicotinamide hydrochloride

The title compound 164 was produced in the same manner as in Example 3.

¹H-NMR (MeOH-d₄, 400 MHz): δ 9.22 (1H, s), 8.87 (1H, d, J=5.4 Hz), 8.83 (1H, d, J=8.04 Hz), 8.43 (1H, d, J=8.32 Hz), 8.25 (1H, s), 7.97-8.04 (1H, m), 7.81 (1H, dd, J=1.24 Hz, J=7.84 Hz), 7.64 (2H, d, J=8.04 Hz), 7.54-7.60 (1H, m), 7.23-7.29 (1H, m), 7.18 (2H, d, J=7.80 Hz), 2.29 (3H, s)

Mass spectrometric value (ESI-MS) 357 (M−1)

Compound 165 N-[2-(3,4-Dimethyl-benzylidene-hydrazinocarbonyl)-phenyl]-nicotinamide hydrochloride

The title compound 165 was produced in the same manner as in Example 3.

¹H-NMR (CDCl₃, 400 MHz): δ 9.92 (1H, s), 9.29 (1H, s), 8.75-8.78 (2H, m), 8.30-8.40 (1H, m), 8.15 (1H, s), 7.55-7.65 (5H, m), 7.42-7.49 (2H, m), 7.15-7.25 (1H, m), 2.32 (3H, s), 2.29 (3H, s)

Mass spectrometric value (ESI-MS) 371 (M−1)

Compound 166 N-[4-Bromo-2-(3-fluoro-benzylidene-hydrazinocarbonyl)-phenyl]-isonicotinamide

The title compound 166 was produced in the same manner as in Example 1.

Mass spectrometric value (ESI-MS) 439 (M−1)

Compound 167 N-[4-Bromo-2-(4-fluoro-benzylidene-hydrazinocarbonyl)-phenyl]-isonicotinamide

The title compound 167 was produced in the same manner as in Example 1.

Mass spectrometric value (ESI-MS) 439 (M−1)

Compound 168 N-[4-Bromo-2-(3-methyl-benzylidene-hydrazinocarbonyl)-phenyl]-isonicotinamide

The title compound 168 was produced in the same manner as in Example 1.

Mass spectrometric value (ESI-MS) 437 (M−1)

Compound 169 N-[4-Bromo-2-(4-methyl-benzylidene-hydrazinocarbonyl)-phenyl]-isonicotinamide

The title compound 169 was produced in the same manner as in Example 1.

Mass spectrometric value (ESI-MS) 435, 437 (M−1)

Compound 170 N-[4-Bromo-2-(3,4-dimethyl-benzylidene-hydrazinocarbonyl)-phenyl]-isonicotinamide

The title compound 170 was produced in the same manner as in Example 1.

Mass spectrometric value (ESI-MS) 451, 452 (M−1)

Compound 171 N-[4-Bromo-2-(4-chloro-3-trifluoromethyl-benzylidene-hydrazinocarbonyl)-phenyl]-isonicotinamide

The title compound 171 was produced in the same manner as in Example 1.

Mass spectrometric value (ESI-MS) 525, 527 (M−1)

Compound 172 N-[4-Bromo-2-(3-fluoro-benzylidene-hydrazinocarbonyl)-phenyl]-nicotinamide

The title compound 172 was produced in the same manner as in Example 1.

Mass spectrometric value (ESI-MS) 441, 442 (M−1)

Compound 173 N-[4-Bromo-2-(4-fluoro-benzylidene-hydrazinocarbonyl)-phenyl]-nicotinamide

The title compound 173 was produced in the same manner as in Example 1.

Mass spectrometric value (ESI-MS) 439 (M−1)

Compound 174 N-[4-Bromo-2-(3-methyl-benzylidene-hydrazinocarbonyl)-phenyl]-nicotinamide

The title compound 174 was produced in the same manner as in Example 1.

Mass spectrometric value (ESI-MS) 435 (M−1)

Compound 175 N-[4-Bromo-2-(4-methyl-benzylidene-hydrazinocarbonyl)-phenyl]-nicotinamide

The title compound 175 was produced in the same manner as in Example 1.

Mass spectrometric value (ESI-MS) 437, 438 (M−1)

Compound 176 N-[4-Bromo-2-(3,4-dimethyl-benzylidene-hydrazinocarbonyl)-phenyl]-nicotinamide

The title compound 176 was produced in the same manner as in Example 1.

Mass spectrometric value (ESI-MS) 451, 452 (M−1)

Compound 177 N-[4-Bromo-2-(4-chloro-3-trifluoromethyl-benzylidene-hydrazinocarbonyl)-phenyl]-nicotinamide

The title compound 177 was produced in the same manner as in Example 1.

Mass spectrometric value (ESI-MS) 524, 525 (M−1)

Compound 178 N-[4-Bromo-2-(3-fluoro-benzylidene-hydrazinocarbonyl)-phenyl]-4-ethyl-benzamide

The title compound 178 was produced in the same manner as in Example 1.

Mass spectrometric value (ESI-MS) 466, 468 (M−1)

Compound 179 N-[4-Bromo-2-(4-fluoro-benzylidene-hydrazinocarbonyl)-phenyl]-4-ethyl-benzamide

The title compound 179 was produced in the same manner as in Example 1.

Mass spectrometric value (ESI-MS) 466 (M−1)

Compound 180 N-[4-Bromo-2-(3-methyl-benzylidene-hydrazinocarbonyl)-phenyl]-4-ethyl-benzamide

The title compound 180 was produced in the same manner as in Example 1.

Mass spectrometric value (ESI-MS) 462 (M−1)

Compound 181 N-[4-Bromo-2-(4-methyl-benzylidene-hydrazinocarbonyl)-phenyl]-4-ethyl-benzamide

The title compound 181 was produced in the same manner as in Example 1.

Mass spectrometric value (ESI-MS) 462, 464 (M−1)

Compound 182 N-[4-Bromo-2-(3,4-dimethyl-benzylidene-hydrazinocarbonyl)-phenyl]-4-ethyl-benzamide

The title compound 182 was produced in the same manner as in Example 1.

Mass spectrometric value (ESI-MS) 476, 478 (M−1)

Compound 183 N-[4-Bromo-2-(4-chloro-3-trifluoromethyl-benzylidene-hydrazinocarbonyl)-phenyl]-4-ethyl-benzamide

The title compound 183 was produced in the same manner as in Example 1.

Mass spectrometric value (ESI-MS) 550 (M−1)

Compound 184 N-[4-Chloro-2-(3-fluoro-benzylidene-hydrazinocarbonyl)-phenyl]-nicotinamide

The title compound 184 was produced in the same manner as in Example 1.

Mass spectrometric value (ESI-MS) 395, 397 (M−1)

Compound 185 N-[4-Chloro-2-(4-fluoro-benzylidene-hydrazinocarbonyl)-phenyl]-nicotinamide

The title compound 185 was produced in the same manner as in Example 1.

Mass spectrometric value (ESI-MS) 395 (M−1)

Compound 186 N-[4-Chloro-2-(3-methyl-benzylidene-hydrazinocarbonyl)-phenyl]-nicotinamide

The title compound 186 was produced in the same manner as in Example 1.

Mass spectrometric value (ESI-MS) 391 (M−1)

Compound 187 N-[4-Chloro-2-(4-methyl-benzylidene-hydrazinocarbonyl)-phenyl]-nicotinamide

The title compound 187 was produced in the same manner as in Example 1.

Mass spectrometric value (ESI-MS) 391 (M−1)

Compound 188 N-[4-Chloro-2-(3,4-dimethyl-benzylidene-hydrazinocarbonyl)-phenyl]-nicotinamide

The title compound 188 was produced in the same manner as in Example 1.

Mass spectrometric value (ESI-MS) 405, 407 (M−1)

Compound 189 N-[4-Chloro-2-(4-chloro-3-trifluoromethyl-benzylidene-hydrazinocarbonyl)-phenyl]-nicotinamide

The title compound 189 was produced in the same manner as in Example 1.

Mass spectrometric value (ESI-MS) 479, 480 (M−1)

Compound 190 N-[4-Chloro-2-(4-fluoro-benzylidene-hydrazinocarbonyl)-phenyl]-isonicotinamide

The title compound 190 was produced in the same manner as in Example 1.

Mass spectrometric value (ESI-MS) 395, 397 (M−1)

Compound 191 N-[4-Chloro-2-(3-methyl-benzylidene-hydrazinocarbonyl)-phenyl]-isonicotinamide

The title compound 191 was produced in the same manner as in Example 1.

Mass spectrometric value (ESI-MS) 391 (M−1)

Compound 192 N-[4-Chloro-2-(4-methyl-benzylidene-hydrazinocarbonyl)-phenyl]-isonicotinamide

The title compound 192 was produced in the same manner as in Example 1.

Mass spectrometric value (ESI-MS) 391 (M−1)

Compound 193 N-[4-Chloro-2-(3,4-dimethyl-benzylidene-hydrazinocarbonyl)-phenyl]-isonicotinamide

The title compound 193 was produced in the same manner as in Example 1.

Mass spectrometric value (ESI-MS) 405 (M−1)

Compound 194 N-[4-Chloro-2-(4-chloro-3-trifluoromethyl-benzylidene-hydrazinocarbonyl)-phenyl]-isonicotinamide

The title compound 194 was produced in the same manner as in Example 1.

Mass spectrometric value (ESI-MS) 479 (M−1)

Example 4 Compound 195 N-[4-Bromo-2-(3-fluoro-benzylidene-hydrazinocarbonyl)-phenyl]-3-(pyridin-4-ylsulfanylmethyl)-benzamide

Methyl 2-amino-5-bromobenzoate (compound A) (2.0 g) was dissolved in anhydrous methylene chloride (40.0 ml). Subsequently, pyridine (1.0 ml) and 3-(chloromethyl)benzoyl chloride (compound B) (2.0 g) were added to the solution at room temperature, and the mixture was stirred at that temperature for 3 hr. After the completion of the reaction, distilled water was added thereto, and the mixture was subjected to separatory extraction with chloroform. The organic layer was washed with a saturated aqueous sodium chloride solution, was dried over sodium sulfate and was then concentrated to give methyl 5-bromo-2-[3-(chloromethyl)benzoyl]aminobenzoate as a useful intermediate (3.32 g, yield 100%).

Subsequently, methyl 5-bromo-2-[3-(chloromethyl)benzoyl]aminobenzoate (1.5 g) was dissolved in anhydrous methylene chloride. Triethylamine (2.0 ml) and 4-mercaptopyridine (compound B′) (880 mg) were added to the solution at room temperature, and the mixture was stirred at that temperature for 12 hr. After the completion of the reaction, distilled water was added thereto at room temperature, and the mixture was subjected to separatory extraction with chloroform. The organic layer was washed with a saturated aqueous sodium chloride solution, was dried over sodium sulfate, and was then concentrated. Diethyl ether was added to the residue for crystallization. The crystals were filtered through Kiriyama Rohto (21 mmφ) and were washed with diethyl ether to give methyl 5-bromo-2-(3-[(4-pyridylsulfanyl)methyl]benzoylamino)benzoate (1.20 g, yield 67%) as a useful intermediate.

Methyl 5-bromo-2-(3-[(4-pyridylsulfanyl)methyl]benzoylamino)-benzoate (1.20 g) obtained by the above reaction was dissolved in ethanol (25.0 ml). Hydrazine monohydrate (2.0 ml) was added to the solution at room temperature, and the mixture was heated under reflux with stirring for one hr. After the completion of the reaction, the reaction solution was allowed to cool at room temperature, was cooled under ice cooling to precipitate crystals. The precipitated crystals were filtered through Kiriyama Rohto (21 mmφ) and were washed with diethyl ether to give N-(4-bromo-2-hydrazinocarbonyl-phenyl)-3-(pyridin-4-ylsulfanylmethyl)-benzamide (753 mg, yield 65.4%) as a hydrazine compound.

N-(4-Bromo-2-hydrazinocarbonyl-phenyl)-3-(pyridin-4-ylsulfanylmethyl)-benzamide (50.0 mg) was dissolved in anhydrous toluene (1.0 ml). Subsequently, a catalytic amount of acetic acid and 3-fluorobenzaldehyde (compound C) (50.0 mg) were added to the solution at room temperature, and the mixture was heated under reflux with stirring for one hr. After the completion of the reaction, the reaction solution was allowed to cool at room temperature and was ice-cooled to precipitate crystals. The precipitated crystals were filtered through Kiriyama Rohto (21 mmφ), were washed with toluene and hexane, and were dried through a vacuum pump to give the title compound 195 (27.0 mg, yield 43.6%).

Mass spectrometric value (ESI-MS) 561, 563 (M−1)

Compound 196 N-[4-Bromo-2-(4-fluoro-benzylidene-hydrazinocarbonyl)-phenyl]-3-(pyridin-4-ylsulfanylmethyl)-benzamide

The title compound 196 was produced in the same manner as in Example 4.

Mass spectrometric value (ESI-MS) 563 (M−1)

Compound 197 N-[4-Bromo-2-(3-methyl-benzylidene-hydrazinocarbonyl)-phenyl]-3-(pyridin-4-ylsulfanylmethyl)-benzamide

The title compound 197 was produced in the same manner as in Example 4.

Mass spectrometric value (ESI-MS) 559 (M−1)

Compound 198 N-[4-Bromo-2-(4-methyl-benzylidene-hydrazinocarbonyl)-phenyl]-3-(pyridin-4-ylsulfanylmethyl)-benzamide

The title compound 198 was produced in the same manner as in Example 4.

Mass spectrometric value (ESI-MS) 559 (M−1)

Compound 199 N-[4-Bromo-2-(3,4-dimethyl-benzylidene-hydrazinocarbonyl)-phenyl]-3-(pyridin-4-ylsulfanylmethyl)-benzamide

The title compound 199 was produced in the same manner as in Example 4.

Mass spectrometric value (ESI-MS) 571 (M−1)

Compound 200 N-[4-Bromo-2-(4-chloro-3-trifluoromethyl-benzylidene-hydrazinocarbonyl)-phenyl]-3-(pyridin-4-ylsulfanylmethyl)-benzamide

The title compound 200 was produced in the same manner as in Example 4.

Mass spectrometric value (ESI-MS) 647 (M−1)

Compound 201 N-[4-Bromo-2-(1-methyl-1H-pyrrol-2-ylmethylene-hydrazinocarbonyl)-phenyl]-3,4-dimethoxy-benzamide

The title compound 201 was produced in the same manner as in Example 1.

Mass spectrometric value (ESI-MS) 484 (M−1)

Compound 202 N-[4-Bromo-2-(4,5-dimethyl-furan-2-ylmethylene-hydrazinocarbonyl)-phenyl]-3,4-dimethoxy-benzamide

The title compound 202 was produced in the same manner as in Example 1.

Mass spectrometric value (ESI-MS) 499 (M−1)

Compound 203 N-[2-(4-Methyl-benzylidene-hydrazinocarbonyl)-phenyl]-isonicotinamide hydrochloride

The title compound 203 was produced in the same manner as in Example 3.

¹H-NMR (CD₃OD, 400 MHz): δ 8.92-8.98 (2H, m), 8.49 (1H, d, J=8.6 Hz), 8.34-8.40 (2H, m), 8.26 (1H, s), 8.81-8.87 (1H, m), 7.64 (2H, d, J=8.0 Hz), 7.55-7.61 (1H, m), 7.25-7.31 (1H, m), 7.15-7.20 (2H, m), 2.30 (3H, s)

Mass spectrometric value (ESI-MS) 357 (M−1)

Compound 204 N-[2-(3-Fluoro-benzylidene-hydrazinocarbonyl)-4-iodo-phenyl]-3,4-dimethoxy-benzamide

The title compound 204 was produced in the same manner as in Example 1.

Mass spectrometric value (ESI-MS) 546 (M−1)

Compound 205 N-[2-(4-Fluoro-benzylidene-hydrazinocarbonyl)-4-iodo-phenyl]-3,4-dimethoxy-benzamide

The title compound 205 was produced in the same manner as in Example 1.

Mass spectrometric value (ESI-MS) 546 (M−1)

Compound 206 N-[4-Iodo-2-(3-methyl-benzylidene-hydrazinocarbonyl)-phenyl]-3,4-dimethoxy-benzamide

The title compound 206 was produced in the same manner as in Example 1.

Mass spectrometric value (ESI-MS) 542 (M−1)

Compound 207 N-[4-Iodo-2-(4-methyl-benzylidene-hydrazinocarbonyl)-phenyl]-3,4-dimethoxy-benzamide

The title compound 207 was produced in the same manner as in Example 1.

Mass spectrometric value (ESI-MS) 542 (M−1)

Compound 208 N-[2-(3,4-Dimethyl-benzylidene-hydrazinocarbonyl)-4-iodo-phenyl]-3,4-dimethoxy-benzamide

The title compound 208 was produced in the same manner as in Example 1.

Mass spectrometric value (ESI-MS) 556 (M−1)

Compound 209 N-[2-(4-Chloro-3-trifluoromethyl-benzylidene-hydrazinocarbonyl)-4-iodo-phenyl]-3,4-dimethoxy-benzamide

The title compound 209 was produced in the same manner as in Example 1.

Mass spectrometric value (ESI-MS) 630 (M−1)

Compound 210 N-[2-(1-Methyl-1H-pyrrol-2-ylmethylene-hydrazinocarbonyl)-phenyl]-isonicotinamide

The title compound 210 was produced in the same manner as in Example 1.

Mass spectrometric value (ESI-MS) 346 (M−1)

Compound 211 N-[4-Bromo-2-(1-methyl-1H-pyrrol-2-ylmethylene-hydrazinocarbonyl)-phenyl]-nicotinamide

The title compound 211 was produced in the same manner as in Example 1.

Mass spectrometric value (ESI-MS) 424 (M−1)

Compound 212 N-[4-Chloro-2-(1-methyl-1H-pyrrol-2-ylmethylene-hydrazinocarbonyl)-phenyl]-nicotinamide

The title compound 212 was produced in the same manner as in Example 1.

Mass spectrometric value (ESI-MS) 380 (M−1)

Compound 213 N-{2-[1-(3-Fluoro-phenyl)-ethylidene-hydrazinocarbonyl]-phenyl}-3,4-dimethoxy-benzamide

The title compound 213 was produced in the same manner as in Example 1.

Mass spectrometric value (ESI-MS) 434 (M−1)

Compound 214 N-{4-Bromo-2-[1-(3-fluoro-phenyl)-ethylidene-hydrazinocarbonyl]-phenyl}-3,4-dimethoxy-benzamide

The title compound 214 was produced in the same manner as in Example 1.

Mass spectrometric value (ESI-MS) 512, 514 (M−1)

Compound 215 N-[4-Bromo-2-(1-m-toluoyl-ethylidene-hydrazinocarbonyl)-phenyl]-nicotinamide

The title compound 215 was produced in the same manner as in Example 1.

Mass spectrometric value (ESI-MS) 449, 451 (M−1)

Compound 216 N-[4-Bromo-2-(1-p-toluoyl-ethylidene-hydrazinocarbonyl)-phenyl]-nicotinamide

The title compound 216 was produced in the same manner as in Example 1.

Mass spectrometric value (ESI-MS) 449 (M−1)

Compound 217 N-[4-Chloro-2-(1-p-toluoyl-ethylidene-hydrazinocarbonyl)-phenyl]-nicotinamide

The title compound 217 was produced in the same manner as in Example 1.

Mass spectrometric value (ESI-MS) 405 (M−1)

Compound 218 N-[2-(4,5-Dimethyl-furan-2-ylmethylene-hydrazinocarbonyl)-phenyl]nicotinamide

The title compound 218 was produced in the same manner as in Example 1.

Mass spectrometric value (ESI-MS) 361 (M−1)

Compound 219 N-[2-(4,5-Dimethyl-furan-2-ylmethylene-hydrazinocarbonyl)-phenyl]-isonicotinamide

The title compound 219 was produced in the same manner as in Example 1.

Mass spectrometric value (ESI-MS) 361 (M−1)

Compound 220 N-[4-Bromo-2-(4,5-dimethyl-furan-2-ylmethylene-hydrazinocarbonyl)-phenyl]-nicotinamide

The title compound 220 was produced in the same manner as in Example 1.

Mass spectrometric value (ESI-MS) 439 (M−1)

Compound 221 N-[4-Bromo-2-(4,5-dimethyl-furan-2-ylmethylene-hydrazinocarbonyl)-phenyl]-isonicotinamide

The title compound 221 was produced in the same manner as in Example 1.

Mass spectrometric value (ESI-MS) 439, 441 (M−1)

Compound 222 N-[4-Chloro-2-(4,5-dimethyl-furan-2-ylmethylene-hydrazinocarbonyl)-phenyl]-nicotinamide

The title compound 222 was produced in the same manner as in Example 1.

Mass spectrometric value (ESI-MS) 395 (M−1)

Compound 223 N-[4-Chloro-2-(4,5-dimethyl-furan-2-ylmethylene-hydrazinocarbonyl)-phenyl]-isonicotinamide

The title compound 223 was produced in the same manner as in Example 1.

Mass spectrometric value (ESI-MS) 395 (M−1)

Compound 224 N-[2-(Benzylidene-hydrazinocarbonyl)-phenyl]-benzamide

The title compound 224 was produced in the same manner as in Example 1.

Mass spectrometric value (ESI-MS) 342 (M−1)

Compound 225 N-[2-(2-Fluoro-benzylidene-hydrazinocarbonyl)-phenyl]-benzamide

The title compound 225 was produced in the same manner as in Example 1.

Mass spectrometric value (ESI-MS) 360 (M−1)

Compound 226 N-[2-(3-Fluoro-benzylidene-hydrazinocarbonyl)-phenyl]-benzamide

The title compound 226 was produced in the same manner as in Example 1.

Mass spectrometric value (ESI-MS) 360 (M−1)

Compound 227 N-[2-(Benzylidene-hydrazinocarbonyl)-4,5-dimethoxy-phenyl]-3,4-dimethoxy-benzamide

The title compound 227 was produced in the same manner as in Example 1.

Mass spectrometric value (ESI-MS) 462 (M−1)

Compound 228 N-[2-(2-Bromo-benzylidene-hydrazinocarbonyl)-phenyl]-benzamide

The title compound 228 was produced in the same manner as in Example 1.

Mass spectrometric value (ESI-MS) 421 (M−1)

Compound 229 N-[2-(2-Methyl-benzylidene-hydrazinocarbonyl)-phenyl]-benzamide

The title compound 229 was produced in the same manner as in Example 1.

Mass spectrometric value (ESI-MS) 356 (M−1)

Compound 230 N-[4,5-Dimethoxy-2-(2-methyl-benzyl idene-hydrazinocarbonyl)-phenyl]-3,4-dimethoxy-benzamide

The title compound 230 was produced in the same manner as in Example 1.

Mass spectrometric value (ESI-MS) 476 (M−1)

Compound 231 N-[2-(2-Chloro-benzylidene-hydrazinocarbonyl)-phenyl]-3,4-dimethoxy-benzamide

The title compound 231 was produced in the same manner as in Example 1.

Mass spectrometric value (ESI-MS) 436 (M−1)

Compound 232 3,4-Dimethoxy-N-[2-(6-methoxy-naphthalen-2-ylmethylene-hydrazinocarbonyl)-phenyl]-benzamide

The title compound 232 was produced in the same manner as in Example 1.

Mass spectrometric value (ESI-MS) 482 (M−1)

Compound 233 N-[2-(Biphenyl-4-ylmethylene-hydrazinocarbonyl)-phenyl]-3,4-dimethoxy-benzamide

The title compound 233 was produced in the same manner as in Example 1.

Mass spectrometric value (ESI-MS) 478 (M−1)

Compound 234 N-[2-(4-Bromo-benzylidene-hydrazinocarbonyl)-phenyl]-3,4-dimethoxy-benzamide

The title compound 234 was produced in the same manner as in Example 1.

Mass spectrometric value (ESI-MS) 480 (M−1)

Compound 235 N-[2-(3-Phenyl-allylidene-hydrazinocarbonyl)-phenyl]-benzamide

The title compound 235 was produced in the same manner as in Example 1.

Mass spectrometric value (ESI-MS) 368 (M−1)

Compound 236 2-Fluoro-N-[2-(2-fluoro-benzylidene-hydrazinocarbonyl)-phenyl]-benzamide

The title compound 236 was produced in the same manner as in Example 1.

Mass spectrometric value (ESI-MS) 378 (M−1)

Compound 237 2-Fluoro-N-[2-(3-fluoro-benzylidene-hydrazinocarbonyl)-phenyl]-benzamide

The title compound 237 was produced in the same manner as in Example 1.

Mass spectrometric value (ESI-MS) 378 (M−1)

Compound 238 2-Fluoro-N-[2-(3-methyl-benzylidene-hydrazinocarbonyl)-phenyl]-benzamide

The title compound 238 was produced in the same manner as in Example 1.

Mass spectrometric value (ESI-MS) 374 (M−1)

Compound 239 N-[2-(3-Tert-butyl-2-hydroxy-benzylidene-hydrazinocarbonyl)-phenyl]-2-fluoro-benzamide

The title compound 239 was produced in the same manner as in Example 1.

Mass spectrometric value (ESI-MS) 432 (M−1)

Compound 240 3,4-Dimethoxy-N-[2-(4-nitro-benzylidene-hydrazinocarbonyl)-phenyl]-benzamide

The title compound 240 was produced in the same manner as in Example 1.

Mass spectrometric value (ESI-MS) 447 (M−1)

Compound 241 N-[2-(4-Diethylamino-benzylidene-hydrazinocarbonyl)-phenyl]-3,4-dimethoxy-benzamide

The title compound 241 was produced in the same manner as in Example 1.

Mass spectrometric value (ESI-MS) 473 (M−1)

Compound 242 N-[2-(3-Fluoro-benzylidene-hydrazinocarbonyl)-4-hydroxy-phenyl]-3,5-dimethoxy-benzamide

The title compound 242 was produced in the same manner as in Example 1.

Mass spectrometric value (ESI-MS) 436, 437 (M−1)

Compound 243 N-[4-Bromo-2-(pyridin-2-ylmethylene-hydrazinocarbonyl)-phenyl]-3,4-dimethoxy-benzamide

The title compound 243 was produced in the same manner as in Example 1.

Mass spectrometric value (ESI-MS) 483 (M−1)

Compound 244 N-[4-Chloro-2-(pyridin-2-ylmethylene-hydrazinocarbonyl)-phenyl]-3,4-dimethoxy-benzamide

The title compound 244 was produced in the same manner as in Example 1.

Mass spectrometric value (ESI-MS) 437 (M−1)

Compound 245 3,4-Dimethoxy-N-[2-pyridin-2-ylmethylene-hydrazinocarbonyl)-phenyl]-benzamide

The title compound 245 was produced in the same manner as in Example 1.

Mass spectrometric value (ESI-MS) 403 (M−1)

Compound 246 N-[4-Chloro-2-(6-methyl-pyridin-2-ylmethylene-hydrazinocarbonyl)-phenyl]-3,4-dimethoxy-benzamide

The title compound 246 was produced in the same manner as in Example 1.

Mass spectrometric value (ESI-MS) 451 (M−1)

Compound 247 3,4-Dimethoxy-N-[2-(6-methyl-pyridin-2-ylmethylene-hydrazinocarbonyl)-phenyl]-benzamide

The title compound 247 was produced in the same manner as in Example 1.

Mass spectrometric value (ESI-MS) 417 (M−1)

Compound 248 N-[4-Bromo-2-(3-methyl-benzylidene-hydrazinocarbonyl)-phenyl]-4-tert-butyl-benzamide

The title compound 248 was produced in the same manner as in Example 1.

Mass spectrometric value (ESI-MS) 490, 492 (M−1)

Compound 249 N-[2-(1-m-Toluyl-ethylidene-hydrazinocarbonyl)-phenyl]-isonicotinamide

The title compound 249 was produced in the same manner as in Example 1.

Mass spectrometric value (ESI-MS) 371 (M−1)

Compound 250 N-[4-Chloro-2-(1-m-toluoyl-ethylidene-hydrazinocarbonyl)-phenyl]-nicotinamide

The title compound 250 was produced in the same manner as in Example 1.

Mass spectrometric value (ESI-MS) 405 (M−1)

Compound 251 N-[2-(1-p-Toluyl-ethylidene-hydrazinocarbonyl)-phenyl]-nicotinamide

The title compound 251 was produced in the same manner as in Example 1.

Mass spectrometric value (ESI-MS) 371 (M−1)

Compound 252 N-[4-Bromo-2-(4-methyl-benzylidene-hydrazinocarbonyl)-phenyl]-nicotinamide hydrochloride

The title compound 252 was produced in the same manner as in Example 3.

¹H-NMR (MeOH-d₄, 400 MHz): δ 9.21-9.25 (1H, m), 8.79-8.93 (2H, m), 8.34-8.39 (1H, m), 8.25 (1H, s), 8.01 (1H, d, J=2.2 Hz), 8.00-8.15 (1H, m), 7.71 (1H, dd, J=8.08 Hz, J=2.20 Hz), 7.63 (2H, d, J=8.32 Hz), 7.18 (2H, d, J=8.08 Hz), 2.29 (3H, s)

Mass spectrometric value (ESI-MS) 437, 438 (M−1)

Compound 253 N-[2-(3-Methyl-benzylidene-hydrazinocarbonyl)-phenyl]-isonicotinamide hydrochloride

The title compound 253 was produced in the same manner as in Example 3.

¹H-NMR (CDCl₃, 400 MHz): δ 8.96-8.99 (2H, m), 8.49 (1H, d, J=8.08 Hz), 8.42 (2H, dd, J=1.20 Hz, J=5.60 Hz), 8.27 (1H, s), 7.85 (1H, dd, J=1.20 Hz, J=7.80 Hz), 7.51-7.61 (3H, m), 7.18-7.31 (3H, m), 2.30 (3H, s)

Mass spectrometric value (ESI-MS) 357 (M−1)

Compound 255 N-[4-Bromo-2-(3-fluoro-benzylidene-hydrazinocarbonyl)-phenyl]-4-(pyridin-4-ylsulfanylmethyl)-benzamide

The title compound 255 was produced in the same manner as in Example 4.

Mass spectrometric value (ESI-MS) 563 (M−1)

Compound 256 N-[4-Bromo-2-(4-fluoro-benzylidene-hydrazinocarbonyl)-phenyl]-4-(pyridin-4-ylsulfanylmethyl)-benzamide

The title compound 256 was produced in the same manner as in Example 4.

Mass spectrometric value (ESI-MS) 563 (M−1)

Compound 257 N-[4-Bromo-2-(3-methyl-benzylidene-hydrazinocarbonyl)-phenyl]-4-(pyridin-4-ylsulfanylmethyl)-benzamide

The title compound 257 was produced in the same manner as in Example 4.

Mass spectrometric value (ESI-MS) 559 (M−1)

Compound 258 N-[4-Bromo-2-(4-methyl-benzylidene-hydrazinocarbonyl)-phenyl]-4-(pyridin-4-ylsulfanylmethyl)-benzamide

The title compound 258 was produced in the same manner as in Example 4.

Mass spectrometric value (ESI-MS) 559 (M−1)

Compound 259 N-[4-Bromo-2-(3,4-dimethyl-benzylidene-hydrazinocarbonyl)-phenyl]-4-(pyridin-4-ylsulfanylmethyl)-benzamide

The title compound 259 was produced in the same manner as in Example 4.

Mass spectrometric value (ESI-MS) 571 (M−1)

Compound 260 N-[4-Bromo-2-(4-chloro-3-trifluoromethyl-benzylidene-hydrazinocarbonyl)-phenyl]-4-(pyridin-4-ylsulfanylmethyl)-benzamide

The title compound 260 was produced in the same manner as in Example 4.

Mass spectrometric value (ESI-MS) 645, 647 (M−1)

Compound 261 N-[4-Bromo-2-(3-fluoro-benzylidene-hydrazinocarbonyl)-phenyl]-4-(2-hydroxy-ethylsulfanylmethyl)-benzamide

The title compound 261 was produced in the same manner as in Example 4.

Mass spectrometric value (ESI-MS) 530 (M−1)

Compound 262 N-[4-Bromo-2-(4-fluoro-benzylidene-hydrazinocarbonyl)-phenyl]-4-(2-hydroxy-ethylsulfanylmethyl)-benzamide

The title compound 262 was produced in the same manner as in Example 4.

Mass spectrometric value (ESI-MS) 530 (M−1)

Compound 263 N-[4-Bromo-2-(3-methyl-benzylidene-hydrazinocarbonyl)-phenyl]-4-(2-hydroxy-ethylsulfanylmethyl)-benzamide

The title compound 263 was produced in the same manner as in Example 4.

Mass spectrometric value (ESI-MS) 524 (M−1)

Compound 264 N-[4-Bromo-2-(4-methyl-benzylidene-hydrazinocarbonyl)-phenyl]-4-(2-hydroxy-ethylsulfanylmethyl)-benzamide

The title compound 264 was produced in the same manner as in Example 4.

Mass spectrometric value (ESI-MS) 526 (M−1)

Compound 265 N-[4-Bromo-2-(3,4-dimethyl-benzylidene-hydrazinocarbonyl)-phenyl]-4-(2-hydroxy-ethylsulfanylmethyl)-benzamide

The title compound 265 was produced in the same manner as in Example 4.

Mass spectrometric value (ESI-MS) 540 (M−1)

Compound 266 N-[4-Bromo-2-(4-chloro-3-trifluoromethyl-benzylidene-hydrazinocarbonyl)-phenyl]-4-(2-hydroxy-ethylsulfanylmethyl)-benzamide

The title compound 266 was produced in the same manner as in Example 4.

Mass spectrometric value (ESI-MS) 612, 614 (M−1)

Compound 267 N-[4-Bromo-2-(3,4-dimethyl-benzylidene-hydrazinocarbonyl)-phenyl]-3-(1H-[1,2,4]triazol-3-ylsulfanylmethyl)-benzamide

The title compound 267 was produced in the same manner as in Example 4.

¹H-NMR (CD₃OD, 400 MHz): δ 8.60 (1H, d, J=9.0 Hz), 8.31 (1H, s), 8.28 (1H, bs), 8.05 (1H, d, J=2.2 Hz), 8.01 (1H, m), 7.86 (1H, m), 7.73 (1H, dd, J=9.0 Hz, J=2.2 Hz), 7.60 (2H, m), 7.52 (1H, m), 7.46 (1H, t, J=7.7 Hz), 7.19 (1H, d, J=7.8 Hz), 4.44 (2H, s), 2.30 (6H, s)

Mass spectrometric value (ESI-MS) 561 (M−1)

Compound 268 N-[4-Bromo-2-(4-methyl-benzylidene-hydrazinocarbonyl)-phenyl]-3-(1H-[1,2,4]triazol-3-ylsulfanylmethyl)-benzamide

The title compound 268 was produced in the same manner as in Example 4.

¹H-NMR (CD₃OD, 400 MHz): δ 2.38 (3H, s), 4.44 (2H, s), 7.26 (1H, d, J=7.4 Hz), 7.46 (2H, m), 7.59 (1H, m), 7.66 (1H, dd, J=9.0 Hz, J=2.4 Hz), 7.72 (1H, m), 7.86 (2H, m), 7.97-8.05 (2H, m), 8.29-8.34 (2H, m), 8.57 (1H, d, J=8.8 Hz)

Mass spectrometric value (ESI-MS) 547 (M−1)

Compound 269 N-[4-Bromo-2-(3-methyl-benzylidene-hydrazinocarbonyl)-phenyl]-3-(1H-[1,2,4]triazol-3-ylsulfanylmethyl)-benzamide

The title compound 269 was produced in the same manner as in Example 4.

¹H-NMR (DMSO-d₆, 400 MHz): δ 2.48-2.53 (3H, m), 4.43 (2H, s), 7.27-7.82 (9H, m), 7.96 (3H, m), 8.57 (1H, d, J=9.0 Hz)

Mass spectrometric value (ESI-MS) 549 (M−1)

Compound 270 N-[4-Bromo-2-(4-fluoro-benzylidene-hydrazinocarbonyl)-phenyl]-3-(1H-[1,2,4]triazol-3-ylsulfanylmethyl)-benzamide

The title compound 270 was produced in the same manner as in Example 4.

¹H-NMR (CD₃OD, 400 MHz): δ 4.44 (2H, s), 7.20 (1H, m), 7.45 (1H, m), 7.59 (1H, m), 7.66 (1H, dd, J=9.0 Hz, J=2.3 Hz), 7.75 (1H, dd, J=9.0 Hz, J=2.3 Hz), 7.87 (2H, m), 7.99-8.06 (3H, m), 8.30 (1H, s), 8.36 (1H, s), 8.57 (1H, m)

Mass spectrometric value (ESI-MS) 553 (M−1)

Compound 271 N-[4-Bromo-2-(3-fluoro-benzylidene-hydrazinocarbonyl)-phenyl]-3-(1H-[1,2,4]triazol-3-ylsulfanylmethyl)-benzamide

The title compound 271 was produced in the same manner as in Example 4.

¹H-NMR (CD₃OD, 400 MHz): δ 4.44 (2H, s), 7.19 (1H, m), 7.45 (2H, m), 7.59-7.77 (3H, m), 7.86 (2H, m), 7.97-8.01 (2H, m), 8.29-8.36 (2H, m), 8.58 (1H, m)

Mass spectrometric value (ESI-MS) 553 (M−1)

Compound 272 N-[4-Bromo-2-(4-chloro-3-trifluoromethyl-benzylidene-hydrazinocarbonyl)-phenyl]-3-(1H-[1,2,4]triazol-3-ylsulfanylmethyl)-benzamide

The title compound 272 was produced in the same manner as in Example 4.

¹H-NMR (CD₃OD, 400 MHz): δ 4.44 (2H, s), 7.45 (1H, m), 7.59 (1H, m), 7.67 (1H, m), 7.76 (1H, dd, J=9.0 Hz, J=2.2 Hz), 7.85 (2H, m), 7.97-8.06 (3H, m), 8.29 (1H, s), 8.39 (1H, s), 8.57 (1H, dd, J=9.0 Hz, J=1.7 Hz)

Mass spectrometric value (ESI-MS) 635 (M−1)

Compound 273 N-[4-Bromo-2-(3,4-dimethyl-benzylidene-hydrazinocarbonyl)-phenyl]-4-(3-hydroxy-propylsulfanylmethyl)-benzamide

The title compound 273 was produced in the same manner as in Example 4.

¹H-NMR (CD₃OD, 400 MHz): δ 1.76 (2H, m), 2.31 (3H, s), 2.32 (3H, s), 2.50 (2H, t, J=7.0 Hz), 3.60 (2H, t, J=6.3 Hz), 3.80 (2H, s), 7.20 (1H, d, J=7.3 Hz), 7.52 (3H, m), 7.66 (1H, s), 7.74 (1H, dd, J=9.0 Hz, J=2.2 Hz), 7.96 (2H, d, J=8.3 Hz), 8.05 (1H, d, J=2.2 Hz), 8.30 (1H, s), 8.63 (1H, d, J=9.0 Hz)

Mass spectrometric value (ESI-MS) 552 (M−1)

Compound 274 N-[4-Bromo-2-(4-methyl-benzylidene-hydrazinocarbonyl)-phenyl]-4-(3-hydroxy-propylsulfanylmethyl)-benzamide

The title compound 274 was produced in the same manner as in Example 4.

¹H-NMR (CD₃OD, 400 MHz): δ 1.76 (2H, m), 2.39 (3H, s), 2.50 (2H, t, J=7.3 Hz), 3.60 (2H, t, J=6.1 Hz), 3.80 (2H, s), 7.27 (2H, d, J=8.1 Hz), 7.52 (2H, d, J=8.0 Hz), 7.74 (3H, m), 7.96 (2H, d, J=8.1 Hz), 8.01 (1H, m), 8.33 (1H, s), 8.63 (1H, d, J=8.8 Hz)

Mass spectrometric value (ESI-MS) 538 (M−1)

Compound 275 N-[4-Bromo-2-(3-methyl-benzylidene-hydrazinocarbonyl)-phenyl]-4-(3-hydroxy-propylsulfanylmethyl)-benzamide

The title compound 275 was produced in the same manner as in Example 4.

¹H-NMR (CD₃OD, 400 MHz): δ 1.76 (2H, m), 2.40 (3H, s), 2.51 (2H, t, J=7.1 Hz), 3.60 (2H, t, J=6.3 Hz), 3.81 (2H, s), 7.25-7.35 (2H, m), 7.52 (2H, m), 7.63 (1H, m), 7.71-7.77 (2H, m), 7.96 (2H, d, J=8.0 Hz), 8.06 (1H, s), 8.34 (1H, s), 8.62 (1H, m)

Mass spectrometric value (ESI-MS) 538 (M−1)

Compound 276 N-[4-Bromo-2-(4-fluoro-benzylidene-hydrazinocarbonyl)-phenyl]-4-(3-hydroxy-propylsulfanylmethyl)-benzamide

The title compound 276 was produced in the same manner as in Example 4.

¹H-NMR (CD₃OD, 400 MHz): δ 1.76 (2H, m), 2.51 (2H, m), 3.60 (2H, m), 3.81 (2H, m), 7.19 (2H, m), 7.51 (2H, m), 7.75-8.06 (6H, m), 8.35 (1H, m), 8.60 (1H, m)

Mass spectrometric value (ESI-MS) 542 (M−1)

Compound 277 N-[4-Bromo-2-(3-fluoro-benzylidene-hydrazinocarbonyl)-phenyl]-4-(3-hydroxy-propylsulfanylmethyl)-benzamide

The title compound 277 was produced in the same manner as in Example 4.

¹H-NMR (CD₃OD, 400 MHz): δ 1.76 (2H, m), 2.51 (2H, t, J=7.3 Hz), 3.60 (2H, t, J=6.4 Hz), 3.81 (2H, s), 7.19 (1H, m), 7.46-7.54 (3H, m), 7.60 (1H, m), 7.70 (1H, m), 7.77 (1H, dd, J=9.1 Hz, J=2.3 Hz), 7.96 (2H, m), 8.07 (1H, s), 8.35 (1H, s), 8.62 (1H, d, J=9.1 Hz)

Mass spectrometric value (ESI-MS) 542 (M−1)

Compound 278 N-[4-Bromo-2-(4-chloro-3-trifluoromethyl-benzylidene-hydrazinocarbonyl)-phenyl]-4-(3-hydroxy-propylsulfanyl methyl)-benzamide

The title compound 278 was produced in the same manner as in Example 4.

¹H-NMR (CD₃OD, 400 MHz): δ 1.76 (2H, m), 2.50 (2H, t, J=7.3 Hz), 3.60 (2H, t, J=6.3 Hz), 3.80 (2H, s), 7.52 (2H, d, J=8.0 Hz), 7.69 (1H, d, J=8.3 Hz), 7.76 (1H, dd, J=8.8 Hz, J=2.0 Hz), 7.95 (2H, d, J=8.3 Hz), 8.05-8.07 (2H, m), 8.33 (1H, s), 8.39 (1H, s), 8.62 (1H, d, J=9.0 Hz)

Mass spectrometric value (ESI-MS) 626 (M−1)

Example 5 Compound 279 N-[4-Bromo-2-(3,4-dimethyl-benzylidene-hydrazinocarbonyl)-phenyl]-3-[(2-morpholin-4-yl-ethylamino)-methyl]-benzamide

Methyl 2-amino-5-bromobenzoate (compound A) (3.0 g) was dissolved in anhydrous methylene chloride (40.0 ml). Subsequently, pyridine (2.1 ml) and 4-(chloromethyl)benzoyl chloride (compound B) (2.2 ml) were added to the solution at room temperature, and the mixture was stirred at that temperature for one hr. After the completion of the reaction, distilled water was added, followed by separatory extraction with chloroform. The organic layer was washed with saturated brine, was dried over sodium sulfate, and was then concentrated to give methyl 5-bromo-2-[3-(chloromethyl)benzoyl]aminobenzoate as a useful intermediate (4.90 g, yield 100%).

Methyl 5-bromo-2-[3-(chloromethyl)benzoyl]aminobenzoate (500 mg) obtained by the above reaction was dissolved in anhydrous methylene chloride (3.0 ml), triethylamine (545 μl) and 4-(2-aminoethyl)morpholine (compound B′) (341 μl) were added to the solution at room temperature, and the mixture was stirred at room temperature for 15 hr. After the completion of the reaction, water was added at room temperature, and the mixture was subjected to separatory extraction with chloroform. The organic layer was washed with saturated brine, dried over sodium sulfate, and was then concentrated. The residue was purified by column chromatography eluted with a chloroform methanol system to give methyl 5-bromo-2-[(3{[(2-morpholinoethyl)amino]methyl}benzoyl)amino]benzoate as a useful intermediate (306 mg, yield 50%).

Methyl 5-bromo-2-[(3{[(2-morpholinoethyl)amino]methyl}benzoyl)-amino]benzoate obtained by the above reaction was dissolved in ethanol (5.0 ml), hydrazine monohydrate (650 μl) was added to the solution, and the mixture was stirred at room temperature for 15 hr. After the completion of the reaction, water was added thereto at room temperature, and the mixture was subjected to separatory extraction with chloroform. The organic layer was washed with saturated brine, was dried over sodium sulfate, and was then concentrated to give N-(4-bromo-2-hydrazinocarbonyl-phenyl)-3-[(2-morpholin-4-yl-ethylamino)-methyl]-benzamide as a hydrazine compound (220 mg, crude yield 75%).

N-(4-Bromo-2-hydrazinocarbonyl-phenyl)-3-[(2-morpholin-4-yl-ethylamino)-methyl]-benzamide (25 mg) was dissolved in anhydrous toluene (1.0 ml), a catalytic amount of acetic acid and 3,4-dimethylbenzaldehyde (compound C) (10.0 μl) were added to the solution at room temperature, and the mixture was stirred at room temperature for 15 hr. After the completion of the reaction, the product was purified by column chromatography eluted with a chloroform methanol system to give the title compound 279 (21.1 mg, yield 67%).

¹H-NMR (CD₃OD, 400 MHz): δ 2.31 (3H, s), 2.32 (3H, s), 2.44 (4H, m), 2.60 (2H, t, J=6.1 Hz), 2.97 (2H, t, J=6.1 Hz), 3.65 (4H, t, J=4.6 Hz), 4.15 (2H, s), 7.20 (1H, d, J=7.8 Hz), 7.54 (1H, m), 7.59-7.70 (3H, m), 7.76 (1H, dd, J=9.0 Hz, J=2.2 Hz), 8.30 (2H, m), 8.07 (1H, d, J=2.2 Hz), 8.32 (1H, s), 8.64 (1H, d, J=9.0 Hz)

Mass spectrometric value (ESI-MS) 594 (M+1)

Compound 280 N-[4-Bromo-2-(3,4-dimethyl-benzylidene-hydrazinocarbonyl)-phenyl]-4-{[(2-diethylamino-ethyl)-methyl-amino]-methyl}-benzamide

The title compound 280 was produced in the same manner as in Example 5.

¹H-NMR (CD₃OD, 400 MHz): δ 1.12 (6H, t, J=7.1 Hz), 2.27 (6H, s), 2.28 (3H, s), 2.60 (2H, t, J=7.3 Hz), 2.77 (4H, q, J=7.3 Hz), 2.88 (2H, t, J=7.3 Hz), 3.63 (2H, s), 7.16 (1H, d, J=7.8 Hz), 7.50 (3H, m), 7.61 (1H, s), 7.70 (1H, dd, J=9.0 Hz, J=2.2 Hz), 7.97 (2H, d, J=8.3 Hz), 8.02 (1H, d, J=2.2 Hz), 8.30 (1H, s), 8.61 (1H, d, J=9.0 Hz)

Mass spectrometric value (ESI-MS) 594 (M+1)

Compound 281 N-[4-Bromo-2-(3,4-dimethyl-benzylidene-hydrazinocarbonyl)-phenyl]-4-[(2-morpholin-4-yl-ethylamino)-methyl]-benzamide

The title compound 281 was produced in the same manner as in Example 5.

¹H-NMR (CDCl₃, 400 MHz): δ 2.29 (3H, s), 2.30 (3H, s), 2.43 (4H, m), 2.54 (2H, t, J=6.0 Hz), 2.72 (2H, t, J=6.0 Hz), 3.70 (4H, t, J=4.6 Hz), 3.89 (2H, s), 7.18 (1H, d, J=7.8 Hz), 7.44-7.70 (6H, m), 7.99 (2H, d, J=7.8 Hz), 8.31 (1H, s), 8.55 (1H, d, J=8.3 Hz)

Mass spectrometric value (ESI-MS) 592 (M+1)

Compound 282 N-[4-Bromo-2-(4-methyl-benzylidene-hydrazinocarbonyl)-phenyl]-4-[(2-morpholin-4-yl-ethylamino)-methyl]-benzamide

The title compound 282 was produced in the same manner as in Example 5.

¹H-NMR (CDCl₃, 400 MHz): δ 2.39 (3H, s), 2.43 (4H, m), 2.53 (2H, t, J=5.9 Hz), 2.72 (2H, t, J=5.9 Hz), 3.70 (4H, t, J=4.6 Hz), 3.89 (2H, s), 7.23 (2H, d, J=8.0 Hz), 7.45 (2H, d, J=8.0 Hz), 7.56 (1H, m), 7.70 (3H, m), 7.99 (2H, m), 8.34 (1H, s), 8.56 (1H, d, J=9.0 Hz)

Mass spectrometric value (ESI-MS) 576 (M−1)

Compound 283 N-[4-Bromo-2-(3-methyl-benzylidene-hydrazinocarbonyl)-phenyl]-4-[(2-morpholin-4-yl-ethylamino)-methyl]-benzamide

The title compound 283 was produced in the same manner as in Example 5.

¹H-NMR (CDCl₃, 400 MHz): δ 2.38 (3H, s), 2.43 (4H, m), 2.52 (2H, t, J=6.0 Hz), 2.70 (2H, t, J=6.0 Hz), 3.70 (4H, t, J=4.4 Hz), 3.88 (2H, s), 7.22-7.32 (2H, m), 7.44 (2H, d, J=8.3 Hz), 7.52 (2H, m), 7.69 (2H, s), 8.00 (2H, d, J=7.8 Hz), 8.42 (2H, m)

Mass spectrometric value (ESI-MS) 578 (M−1)

Compound 284 N-[4-Bromo-2-(4-fluoro-benzylidene-hydrazinocarbonyl)-phenyl]-4-[(2-morpholin-4-yl-ethylamino)-methyl]-benzamide

The title compound 284 was produced in the same manner as in Example 5.

¹H-NMR (CDCl₃, 400 MHz): δ 2.43 (4H, m), 2.52 (2H, t, J=6.0 Hz), 2.70 (2H, t, J=6.0 Hz), 3.70 (4H, t, J=4.5 Hz), 3.89 (2H, s), 7.12 (2H, m), 7.45 (2H, d, J=8.3 Hz), 7.54 (1H, m), 7.67 (1H, m), 7.82 (2H, m), 8.00 (2H, d, J=7.8 Hz), 8.39 (1H, s), 8.48 (1H, m)

Mass spectrometric value (ESI-MS) 582 (M−1)

Compound 285 N-[4-Bromo-2-(4-methyl-benzylidene-hydrazinocarbonyl)-phenyl]-4-{[(2-diethylamino-ethyl)-methyl-amino]-methyl}-benzamide

The title compound 285 was produced in the same manner as in Example 5.

¹H-NMR (CDCl₃, 400 MHz): δ 1.04 (6H, t, J=7.2 Hz), 2.21 (3H, s), 2.33 (3H, s), 2.51-2.66 (8H, m), 3.55 (2H, s), 7.18 (2H, d, J=8.0 Hz), 7.43 (3H, m), 7.66 (2H, d, J=8.0 Hz), 7.74 (1H, m), 7.98 (2H, d, J=8.0 Hz), 8.36 (1H, d, J=9.0 Hz), 8.49 (1H, s)

Mass spectrometric value (ESI-MS) 576 (M−1)

Compound 286 N-[4-Bromo-2-(3-methyl-benzylidene-hydrazinocarbonyl)-phenyl]-4-{[(2-diethylamino-ethyl)-methyl-amino]-methyl}-benzamide

The title compound 286 was produced in the same manner as in Example 5.

¹H-NMR (CDCl₃, 400 MHz): δ 1.04 (6H, t, J=7.1 Hz), 2.23 (3H, s), 2.40 (3H, s), 2.52-2.66 (8H, m), 3.59 (2H, s), 7.24-7.33 (2H, m), 7.45 (2H, d, J=8.3 Hz), 7.56 (2H, m), 7.70 (2H, m), 8.00 (2H, d, J=7.6 Hz), 8.38 (1H, s), 8.50 (1H, d, J=9.0 Hz)

Mass spectrometric value (ESI-MS) 578 (M−1)

Compound 287 N-[4-Bromo-2-(4-fluoro-benzylidene-hydrazinocarbonyl)-phenyl]-4-{[(2-diethylamino-ethyl)-methyl-amino]-methyl}-benzamide

The title compound 287 was produced in the same manner as in Example 5.

¹H-NMR (CDCl₃, 400 MHz): δ 1.04 (6H, t, J=7.1 Hz), 2.23 (3H, s), 2.54-2.66 (8H, m), 3.59 (2H, s), 7.12 (2H, m), 7.45 (2H, d, J=8.3 Hz), 7.54 (1H, m), 7.68 (1H, s), 7.83 (2H, m), 7.99 (2H, d, J=7.8 Hz), 8.42 (1H, s), 8.47 (1H, d, J=9.0 Hz)

Mass spectrometric value (ESI-MS) 580 (M−1)

Compound 288 N-[4-Bromo-2-(3-fluoro-benzylidene-hydrazinocarbonyl)-phenyl]-4-{[(2-diethylamino-ethyl)-methyl-amino]-methyl}-benzamide

The title compound 288 was produced in the same manner as in Example 5.

¹H-NMR (CDCl₃, 400 MHz): δ 1.04 (6H, t, J=7.1 Hz), 2.22 (3H, s), 2.52-2.66 (8H, m), 3.58 (2H, s), 7.10 (1H, m), 7.34-7.46 (4H, m), 7.55 (2H, m), 7.68 (1H, s), 7.99 (2H, d, J=7.8 Hz), 8.29 (1H, d, J=8.8 Hz), 8.52 (1H, s)

Mass spectrometric value (ESI-MS) 582 (M−1)

Compound 289 N-[4-Bromo-2-(4-chloro-3-trifluoromethyl-benzylidene-hydrazinocarbonyl)-phenyl]-4-{[(2-diethylamino-ethyl)-methyl-amino]-methyl}-benzamide

The title compound 289 was produced in the same manner as in Example 5.

¹H-NMR (CDCl₃, 400 MHz): δ 1.04 (6H, t, J=7.1 Hz), 2.23 (3H, s), 2.53-2.66 (8H, m), 3.60 (2H, s), 7.48 (3H, m), 7.58 (1H, d, J=8.3 Hz), 7.67 (1H, s), 7.98-8.07 (4H, m), 8.56 (1H, m), 8.52 (1H, m)

Mass spectrometric value (ESI-MS) 664 (M−1)

Compound 290 N-[4-Bromo-2-(4-methoxy-benzylidene-hydrazinocarbonyl)-phenyl]-4-{[(2-diethylamino-ethyl)-methyl-amino]-methyl}-benzamide

The title compound 290 was produced in the same manner as in Example 5.

¹H-NMR (CDCl₃, 400 MHz): δ 1.04 (6H, t, J=7.1 Hz), 2.21 (3H, s), 2.51-2.66 (8H, m), 3.56 (2H, s), 3.80 (3H, s), 6.89 (2H, d, J=8.8 Hz), 7.43 (3H, m), 7.71 (3H, m), 7.98 (2H, d, J=8.0 Hz), 8.38 (1H, d, J=9.0 Hz), 8.45 (1H, s)

Mass spectrometric value (ESI-MS) 594 (M−1)

Compound 291 N-[4-Bromo-2-(3-methoxy-benzylidene-hydrazinocarbonyl)-phenyl]-4-{[(2-diethylamino-ethyl)-methyl-amino]-methyl}-benzamide

The title compound 291 was produced in the same manner as in Example 5.

¹H-NMR (CDCl₃, 400 MHz): δ 1.03 (6H, t, J=7.1 Hz), 2.21 (3H, s), 2.51-2.65 (8H, m), 3.56 (2H, s), 3.84 (3H, s), 6.94 (1H, m), 7.27-7.48 (6H, m), 7.75 (1H, s), 7.97 (2H, d, J=7.8 Hz), 8.41 (1H, d, J=9.0 Hz), 8.47 (1H, s)

Mass spectrometric value (ESI-MS) 592 (M−1)

Compound 292 N-[4-Bromo-2-(3,4-dimethyl-benzylidene-hydrazinocarbonyl)-phenyl]-4-[(2-diethylamino-ethylamino)-methyl]-benzamide

The title compound 292 was produced in the same manner as in Example 5.

¹H-NMR (CDCl₃, 400 MHz): δ 1.05 (6H, t, J=7.2 Hz), 2.29 (3H, s), 2.30 (3H, s), 2.57-2.73 (8H, m), 3.87 (3H, s), 7.18 (1H, d, J=7.8 Hz), 7.43-7.73 (6H, m), 7.99 (2H, d, J=7.8 Hz), 8.31 (1H, s), 8.56 (1H, d, J=9.0 Hz)

Mass spectrometric value (ESI-MS) 576 (M−1)

Compound 293 N-[4-Bromo-2-(4-methyl-benzylidene-hydrazinocarbonyl)-phenyl]-4-[(2-diethylamino-ethylamino)-methyl]benzamide

The title compound 293 was produced in the same manner as in Example 5.

¹H-NMR (CDCl₃, 400 MHz): δ 1.05 (6H, t, J=7.1 Hz), 2.39 (3H, s), 2.56-2.73 (8H, m), 3.87 (2H, s), 7.22-7.27 (2H, m), 7.44 (2H, d, J=8.3 Hz), 7.57-7.71 (4H, m), 7.99 (2H, m), 8.34 (1H, s), 8.59 (1H, d, J=9.0 Hz)

Mass spectrometric value (ESI-MS) 562 (M−1)

Compound 294 N-[4-Bromo-2-(3-methyl-benzylidene-hydrazinocarbonyl)-phenyl]-4-[(2-diethylamino-ethylamino)-methyl]-benzamide

The title compound 294 was produced in the same manner as in Example 5.

¹H-NMR (CDCl₃, 400 MHz): δ 1.03 (6H, t, J=7.1 Hz), 2.39 (3H, s), 2.52-2.70 (8H, m), 3.87 (2H, s), 7.23-7.33 (2H, m), 7.45 (2H, d, J=8.3 Hz), 7.55 (2H, m), 7.70 (2H, m), 8.00 (2H, d, J=7.8 Hz), 8.38 (1H, s), 8.51 (1H, d, J=9.0 Hz)

Mass spectrometric value (ESI-MS) 562 (M−1)

Compound 295 N-[4-Bromo-2-(4-fluoro-benzylidene-hydrazinocarbonyl)-phenyl]-4-[(2-diethylamino-ethylamino)-methyl]benzamide

The title compound 295 was produced in the same manner as in Example 5.

¹H-NMR (CDCl₃, 400 MHz): δ 1.05 (6H, t, J=7.1 Hz), 2.55-2.72 (8H, m), 3.87 (2H, s), 7.12 (2H, m), 7.45 (2H, d, J=8.1 Hz), 7.56-7.82 (4H, m), 7.99 (2H, d, J=7.6 Hz), 8.39 (1H, s), 8.55 (1H, d, J=8.6 Hz)

Mass spectrometric value (ESI-MS) 568 (M−1)

Compound 296 N-[4-Bromo-2-(3-fluoro-benzylidene-hydrazinocarbonyl)-phenyl]-4-[(2-diethylamino-ethylamino)-methyl]-benzamide

The title compound 296 was produced in the same manner as in Example 5.

¹H-NMR (CDCl₃, 400 MHz): δ 1.04 (6H, t, J=7.1 Hz), 2.53-2.71 (8H, m), 3.88 (2H, s), 7.13 (1H, m), 7.37-7.71 (7H, m), 7.99 (2H, d, J=7.6 Hz), 8.42 (1H, s), 8.49 (1H, d, J=8.8 Hz)

Mass spectrometric value (ESI-MS) 568 (M−1)

Compound 297 N-[4-Bromo-2-(4-chloro-3-trifluoromethyl-benzylidene-hydrazinocarbonyl)-phenyl]-4-[(2-diethylamino-ethylamino)-methyl]-benzamide

The title compound 297 was produced in the same manner as in Example 5.

¹H-NMR (CDCl₃, 400 MHz): δ 1.05 (3H, t, J=7.1 Hz), 1.24 (3H, m), 2.53-2.75 (6H, m), 3.72 (2H, m), 3.87 (2H, s), 7.46 (2H, d, J=7.8 Hz), 7.56 (3H, m), 7.73 (1H, m), 7.98 (3H, m), 8.06 (1H, s), 8.48 (1H, d, J=8.3 Hz)

Mass spectrometric value (ESI-MS) 650 (M−1)

Compound 298 N-[4-Bromo-2-(4-methoxy-benzylidene-hydrazinocarbonyl)-phenyl]-4-[(2-diethylamino-ethylamino)-methyl]-benzamide

The title compound 298 was produced in the same manner as in Example 5.

¹H-NMR (CDCl₃, 400 MHz): δ 1.05 (6H, t, J=7.2 Hz), 2.55-2.72 (8H, m), 3.85 (3H, s), 3.87 (2H, s), 6.93 (2H, d, J=8.8 Hz), 7.44 (2H, d, J=8.0 Hz), 7.58 (1H, m), 7.75 (3H, m), 7.99 (2H, d, J=7.6 Hz), 8.31 (1H, s), 8.60 (1H, d, J=9.0 Hz)

Mass spectrometric value (ESI-MS) 578 (M−1)

Compound 299 N-[4-Bromo-2-(3-methoxy-benzylidene-hydrazinocarbonyl)-phenyl]-4-[(2-diethylamino-ethylamino)-methyl]-benzamide

The title compound 299 was produced in the same manner as in Example 5.

¹H-NMR (CDCl₃, 400 MHz): δ 1.03 (6H, t, J=7.1 Hz), 2.52-2.70 (8H, m), 3.86 (3H, s), 3.87 (2H, s), 6.97 (1H, m), 7.29-7.45 (5H, m), 7.56 (1H, s), 7.73 (1H, m), 7.99 (2H, d, J=8.0 Hz), 8.39 (1H, s), 8.53 (1H, m)

Mass spectrometric value (ESI-MS) 578 (M−1)

Compound 300 4-({3-[Bis-(2-hydroxy-ethyl)-amino]-propylamino}-methyl)-N-[4-bromo-2-(3,4-dimethyl-benzylidene-hydrazinocarbonyl)-phenyl]-benzamide

The title compound 300 was produced in the same manner as in Example 5.

¹H-NMR (CD₃OD, 400 MHz): δ 1.73 (2H, m), 2.29 (3H, s), 2.30 (3H, s), 2.61 (6H, m), 2.73 (2H, t, J=6.8 Hz), 3.60 (4H, m), 3.89 (2H, s), 7.18 (1H, d, J=7.6 Hz), 7.53 (3H, m), 7.64 (1H, s), 7.71 (1H, dd, J=8.8 Hz, J=2.4 Hz), 7.98-8.05 (3H, m), 8.29 (1H, s), 8.60 (1H, d, J=9.0 Hz)

Mass spectrometric value (ESI-MS) 626 (M+1)

Compound 301 4-({3-[Bis-(2-hydroxy-ethyl)-amino]-propylamino}-methyl)-N-[4-bromo-2-(3-fluoro-benzylidene-hydrazinocarbonyl)-phenyl]-benzamide

The title compound 301 was produced in the same manner as in Example 5.

¹H-NMR (CD₃OD, 400 MHz): δ 1.74 (2H, m), 2.63 (6H, m), 2.75 (2H, m), 3.61 (4H, m), 3.90 (2H, s), 7.17 (1H, m), 7.45 (1H, m), 7.33-7.72 (5H, m), 7.89 (2H, m), 8.09 (1H, d, J=2.4 Hz), 8.35 (1H, s), 8.60 (1H, d, J=8.8 Hz)

Mass spectrometric value (ESI-MS) 612 (M−1)

Compound 302 4-({3-[Bis-(2-hydroxy-ethyl)-amino]-propylamino}-methyl)-N-[4-bromo-2-(4-chloro-3-trifluoromethyl-benzylidene-hydrazinocarbonyl)-phenyl]-benzamide

The title compound 302 was produced in the same manner as in Example 5.

¹H-NMR (CD₃OD, 400 MHz): δ 1.75 (2H, m), 2.63 (6H, m), 2.78 (2H, m), 3.61 (4H, m), 3.91 (2H, s), 7.54 (2H, d, J=8.0 Hz), 7.66 (2H, m), 8.00 (3H, m), 8.11 (1H, d, J=2.4 Hz), 8.32 (1H, s), 8.38 (1H, s), 8.58 (1H, d, J=8.8 Hz)

Mass spectrometric value (ESI-MS) 696 (M−1)

Compound 303 4-{[Bis-(2-hydroxy-propyl)-amino]-methyl}-N-[4-bromo-2-(3,4-dimethyl-benzylidene-hydrazinocarbonyl)-phenyl]-benzamide

The title compound 303 was produced in the same manner as in Example 5.

¹H-NMR (CDCl₃, 400 MHz): δ 1.11 (3H, s), 1.13 (3H, s), 2.29 (6H, m), 2.45-2.65 (4H, m), 3.60-3.99 (4H, m), 7.18 (1H, d, J=7.8 Hz), 7.47 (3H, m), 7.55 (1H, m), 7.64 (1H, s), 7.70 (1H, s), 8.01 (2H, d, J=7.6 Hz), 8.31 (1H, s), 8.52 (1H, d, J=8.6 Hz)

Mass spectrometric value (ESI-MS) 595 (M−1)

Compound 304 4-{[Bis-(2-hydroxy-propyl)-amino]-methyl}-N-[4-bromo-2-(4-methyl-benzylidene-hydrazinocarbonyl)-phenyl]-benzamide

The title compound 304 was produced in the same manner as in Example 5.

¹H-NMR (CDCl₃, 400 MHz): δ 1.11 (6H, m), 2.34 (3H, s), 2.42-2.62 (4H, m), 3.59-3.93 (4H, m), 7.19 (2H, d, J=8.0 Hz), 7.44 (3H, m), 7.68 (3H, m), 7.98 (2H, d, J=7.8 Hz), 8.41 (2H, m)

Mass spectrometric value (ESI-MS) 579 (M−1)

Compound 305 N-[4-Bromo-2-(3,4-dimethyl-benzylidene-hydrazinocarbonyl)-phenyl]-4-[4-(2-morpholin-4-yl-2-oxo-ethyl)-piperazin-1-ylmethyl]-benzamide

The title compound 305 was produced in the same manner as in Example 5.

¹H-NMR (CDCl₃, 400 MHz): δ 2.26 (3H, s), 2.28 (3H, s), 2.49 (8H, m), 3.16 (2H, s), 3.49-3.70 (10H, m), 7.15 (1H, d, J=7.8 Hz), 7.40-7.52 (4H, m), 7.62 (1H, s), 7.73 (1H, s), 7.96 (2H, d, J=7.8 Hz), 8.38 (1H, s), 8.49 (1H, d, J=8.8 Hz)

Mass spectrometric value (ESI-MS) 673 (M−1)

Compound 306 N-[4-Bromo-2-(4-chloro-3-trifluoromethyl-benzylidene-hydrazinocarbonyl)-phenyl]-4-[4-(2-morpholin-4-yl-2-oxo-ethyl)-piperazin-1-ylmethyl]-benzamide

The title compound 306 was produced in the same manner as in Example 5.

¹H-NMR (CDCl₃, 400 MHz): δ 2.50 (8H, m), 3.15 (2H, s), 3.49-3.75 (10H, m), 7.42 (2H, m), 7.54 (2H, m), 7.71 (1H, s), 7.99 (4H, m), 8.44 (1H, d, J=8.5 Hz), 8.51 (1H, s)

Mass spectrometric value (ESI-MS) 747 (M−1)

Compound 307 N-[4-Bromo-2-(4-methoxy-benzylidene-hydrazinocarbonyl)-phenyl]-4-[4-(2-morpholin-4-yl-2-oxo-ethyl)-piperazin-1-ylmethyl]-benzamide

The title compound 307 was produced in the same manner as in Example 5.

¹H-NMR (CDCl₃, 400 MHz): δ 2.48 (8H, m), 3.16 (2H, s), 3.48-3.75 (10H, m), 3.81 (3H, s), 6.89 (2H, d, J=8.8 Hz), 7.39 (2H, d, J=8.1 Hz), 7.50 (1H, m), 7.69-7.53 (3H, m), 7.96 (2H, d, J=8.0 Hz), 8.40 (1H, s), 8.49 (1H, d, J=9.0 Hz)

Mass spectrometric value (ESI-MS) 675 (M−1)

Compound 308 4-[1,4′]Bipiperidinyl-1′-ylmethyl-N-[4-bromo-2-(3,4-dimethyl-benzylidene-hydrazinocarbonyl)-phenyl]-benzamide

The title compound 308 was produced in the same manner as in Example 5.

¹H-NMR (CDCl₃, 400 MHz): δ 1.47 (2H, m), 1.65 (6H, m), 1.82 (2H, m), 1.94 (2H, t, J=11.2 Hz), 2.24 (3H, s), 2.26 (3H, s), 2.55-2.68 (5H, m), 2.87 (2H, d, J=11.5 Hz), 3.47 (2H, s), 7.13 (1H, d, J=7.8 Hz), 7.36 (2H, d, J=8.0 Hz), 7.43 (1H, d, J=7.8 Hz), 7.50 (1H, d, J=8.8 Hz), 7.59 (1H, s), 7.88 (1H, s), 7.96 (2H, d, J=8.0 Hz), 8.43 (1H, s), 8.53 (1H, d, J=9.0 Hz)

Mass spectrometric value (ESI-MS) 630 (M−1)

Compound 309 4-[1,4′]Bipiperidinyl-t-ylmethyl-N-[4-bromo-2-(4-methyl-benzylidene-hydrazinocarbonyl)-phenyl]-benzamide

The title compound 309 was produced in the same manner as in Example 5.

¹H-NMR (CDCl₃, 400 MHz): δ 1.47 (2H, m), 1.59-1.73 (6H, m), 1.82 (2H, m), 1.93 (2H, m), 2.34 (3H, s), 2.57-2.69 (5H, m), 2.87 (2H, d, J=11.5 Hz), 3.47 (2H, s), 7.19 (2H, d, J=8.0 Hz), 7.36 (2H, d, J=8.0 Hz), 7.51 (1H, m), 7.66 (2H, d, J=8.0 Hz), 7.87 (1H, s), 7.96 (2H, d, J=8.0 Hz), 8.45 (1H, s), 8.53 (1H, d, J=9.0 Hz)

Mass spectrometric value (ESI-MS) 614 (M−1)

Compound 310 4-[1,4′]Bipiperidinyl-t-ylmethyl-N-[4-bromo-2-(3-methyl-benzylidene-hydrazinocarbonyl)-phenyl]-benzamide

The title compound 310 was produced in the same manner as in Example 5.

¹H-NMR (CDCl₃, 400 MHz): δ 1.47 (2H, m), 1.59-1.74 (6H, m), 1.83 (2H, m), 1.94 (2H, m), 2.35 (3H, s), 2.59-2.75 (5H, m), 2.87 (2H, d, J=11.5 Hz), 3.47 (2H, s), 7.19 (1H, d, J=7.6 Hz), 7.26 (1H, m), 7.36 (2H, d, J=8.1 Hz), 7.51 (2H, m), 7.64 (1H, s), 7.90 (1H, s), 7.95 (2H, d, J=8.1 Hz), 8.46 (1H, s), 8.54 (1H, d, J=8.8 Hz)

Mass spectrometric value (ESI-MS) 614 (M−1)

Compound 311 4-[1,4′]Bipiperidinyl-t-ylmethyl-N-[4-bromo-2-(4-fluoro-benzylidene-hydrazinocarbonyl)-phenyl]-benzamide

The title compound 311 was produced in the same manner as in Example 5.

¹H-NMR (CDCl₃, 400 MHz): δ 1.47 (2H, m), 1.60-1.75 (6H, m), 1.83 (2H, m), 1.93 (2H, m), 2.56-2.74 (5H, m), 2.87 (2H, d, J=11.2 Hz), 3.47 (2H, s), 7.06 (2H, t, J=8.5 Hz), 7.36 (2H, d, J=8.1 Hz), 7.50 (1H, d, J=8.3 Hz), 7.74 (2H, m), 7.87-8.00 (3H, m), 8.50 (2H, m)

Mass spectrometric value (ESI-MS) 620 (M−1)

Compound 312 4-[1,4′]Bipiperidinyl-1′-ylmethyl-N-[4-bromo-2-(3-fluoro-benzylidene-hydrazinocarbonyl)-phenyl]-benzamide

The title compound 312 was produced in the same manner as in Example 5.

¹H-NMR (CDCl₃, 400 MHz): δ 1.47 (2H, m), 1.59-1.75 (6H, m), 1.83 (2H, m), 1.94 (2H, m), 2.50-2.70 (5H, m), 2.87 (2H, d, J=11.2 Hz), 3.48 (2H, s), 7.08 (1H, m), 7.30-7.40 (3H, m), 7.50 (3H, m), 7.87 (1H, s), 7.95 (2H, d, J=8.1 Hz), 8.49 (2H, m)

Mass spectrometric value (ESI-MS) 620 (M−1)

Compound 313 4-[1,4′]Bipiperidinyl-1′-ylmethyl-N-[4-bromo-2-(4-chloro-3-trifluoromethyl-benzylidene-hydrazinocarbonyl)-phenyl]-benzamide

The title compound 313 was produced in the same manner as in Example 5.

¹H-NMR (CDCl₃, 400 MHz): δ 1.50 (2H, m), 1.60-1.80 (6H, m), 1.82-1.96 (4H, m), 2.62-2.78 (5H, m), 2.86 (2H, d, J=11.0 Hz), 3.46 (2H, s), 7.35 (2H, d, J=8.0 Hz), 7.51 (2H, d, J=8.6 Hz), 7.94 (5H, m), 8.50 (1H, d, J=9.0 Hz), 8.57 (1H, s)

Mass spectrometric value (ESI-MS) 702 (M−1)

Compound 314 4-[1,4′]Bipiperidinyl-1′-ylmethyl-N-[4-bromo-2-(4-methoxy-benzylidene-hydrazinocarbonyl)-phenyl]-benzamide

The title compound 314 was produced in the same manner as in Example 5.

¹H-NMR (CDCl₃, 400 MHz): δ 1.47 (2H, m), 1.59-1.75 (6H, m), 1.83 (2H, m), 1.94 (2H, m), 2.60-2.76 (5H, m), 2.87 (2H, d, J=11.5 Hz), 3.46 (2H, s), 3.79 (3H, s), 6.88 (2H, d, J=8.6 Hz), 7.35 (2H, d, J=8.0 Hz), 7.52 (1H, d, J=9.0 Hz), 7.68 (2H, d, J=8.6 Hz), 7.90 (1H, s), 7.95 (2H, d, J=8.0 Hz), 8.41 (1H, s), 8.55 (1H, d, J=9.0 Hz)

Mass spectrometric value (ESI-MS) 632 (M−1)

Compound 315 4-[1,4′]Bipiperidinyl-1′-ylmethyl-N-[4-bromo-2-(3-methoxy-benzylidene-hydrazinocarbonyl)-phenyl]-benzamide

The title compound 315 was produced in the same manner as in Example 5.

¹H-NMR (CDCl₃, 400 MHz): δ 1.47 (2H, m), 1.58-1.80 (6H, m), 1.83 (2H, m), 1.92 (2H, m), 2.59-2.75 (5H, m), 2.85 (2H, m), 3.45 (2H, s), 3.82 (3H, s), 6.91 (1H, d, J=6.8 Hz), 7.20-7.40 (5H, m), 7.52 (1H, d, J=9.0 Hz), 7.94 (3H, m), 8.49 (1H, s), 8.56 (1H, d, J=9.0 Hz)

Mass spectrometric value (ESI-MS) 632 (M−1)

Compound 316 N-[4-Bromo-2-(3,4-dimethyl-benzylidene-hydrazinocarbonyl)-phenyl]-4-[4-(2-hydroxy-ethyl)-piperazin-1-ylmethyl]-benzamide

The title compound 316 was produced in the same manner as in Example 5.

¹H-NMR (CDCl₃, 400 MHz): δ 2.29 (3H, s), 2.30 (3H, s), 2.48-2.65 (10H, m), 3.58 (2H, s), 3.64 (2H, t, J=5.2 Hz), 7.18 (1H, d, J=7.8 Hz), 7.46 (3H, m), 7.57 (1H, d, J=9.0 Hz), 7.64 (1H, s), 7.70 (1H, s), 7.98 (2H, d, J=7.8 Hz), 8.29 (1H, s), 8.56 (1H, d, J=9.0 Hz)

Mass spectrometric value (ESI-MS) 592 (M−1)

Compound 317 N-[4-Bromo-2-(4-methyl-benzylidene-hydrazinocarbonyl)-phenyl]-4-[4-(2-hydroxy-ethyl)-piperazin-1-ylmethyl]-benzamide

The title compound 317 was produced in the same manner as in Example 5.

¹H-NMR (CDCl₃, 400 MHz): δ 2.40 (3H, s), 2.54-2.75 (10H, m), 3.60 (2H, s), 3.68 (2H, m), 7.25 (2H, m), 7.45 (2H, d, J=8.0 Hz), 7.62 (1H, m), 7.70 (3H, m), 7.98 (2H, d, J=8.0 Hz), 8.28 (1H, s), 8.64 (1H, d, J=9.0 Hz)

Mass spectrometric value (ESI-MS) 576 (M−1)

Compound 318 N-[4-Bromo-2-(3-methyl-benzylidene-hydrazinocarbonyl)-phenyl]-4-[4-(2-hydroxy-ethyl)-piperazin-1-ylmethyl]-benzamide

The title compound 318 was produced in the same manner as in Example 5.

¹H-NMR (CDCl₃, 400 MHz): δ 2.40 (3H, s), 2.50-2.67 (10H, m), 3.58 (2H, s), 3.64 (2H, t, J=5.3 Hz), 7.24 (1H, m), 7.32 (1H, m), 7.45 (2H, d, J=8.0 Hz), 7.56 (2H, m), 7.70 (2H, m), 7.99 (2H, d, J=8.0 Hz), 8.34 (1H, s), 8.53 (1H, d, J=9.2 Hz)

Mass spectrometric value (ESI-MS) 578 (M−1)

Compound 319 N-[4-Bromo-2-(4-fluoro-benzylidene-hydrazinocarbonyl)-phenyl]-4-[4-(2-hydroxy-ethyl)-piperazin-1-ylmethyl]-benzamide

The title compound 319 was produced in the same manner as in Example 5.

¹H-NMR (CDCl₃, 400 MHz): δ 2.48-2.70 (10H, m), 3.58 (2H, s), 3.65 (2H, t, J=5.2 Hz), 7.12 (2H, m), 7.45 (2H, d, J=8.0 Hz), 7.53 (1H, m), 7.68 (1H, s), 7.82 (2H, m), 7.98 (2H, d, J=8.0 Hz), 8.40 (1H, s), 8.46 (1H, d, J=8.8 Hz)

Mass spectrometric value (ESI-MS) 580 (M−1)

Compound 320 N-[4-Bromo-2-(3-fluoro-benzylidene-hydrazinocarbonyl)-phenyl]-4-[4-(2-hydroxy-ethyl)-piperazin-1-ylmethyl]-benzamide

The title compound 320 was produced in the same manner as in Example 5.

¹H-NMR (CDCl₃, 400 MHz): δ 2.50-2.75 (10H, m), 3.60 (2H, s), 3.69 (2H, t, J=5.2 Hz), 7.14 (1H, m), 7.36-7.72 (7H, m), 7.98 (2H, d, J=8.0 Hz), 8.39 (1H, s), 8.50 (1H, d, J=9.0 Hz)

Mass spectrometric value (ESI-MS) 582 (M−1)

Compound 321 N-[4-Bromo-2-(4-chloro-3-trifluoromethyl-benzylidene-hydrazinocarbonyl)-phenyl]-4-[4-(2-hydroxy-ethyl)-piperazin-1-ylmethyl]-benzamide

The title compound 321 was produced in the same manner as in Example 5.

¹H-NMR (CDCl₃, 400 MHz): δ 2.50-2.72 (10H, m), 3.60 (2H, s), 3.66 (2H, t, J=5.2 Hz), 7.15 (1H, m), 7.43-7.72 (6H, m), 7.99 (2H, d, J=8.0 Hz), 8.07 (1H, s), 8.46 (1H, m)

Mass spectrometric value (ESI-MS) 664 (M−1)

Compound 322 N-[4-Bromo-2-(4-methoxy-benzylidene-hydrazinocarbonyl)-phenyl]-4-[4-(2-hydroxy-ethyl)-piperazin-1-ylmethyl]-benzamide

The title compound 322 was produced in the same manner as in Example 5.

¹H-NMR (CDCl₃, 400 MHz): δ 2.50-2.70 (10H, m), 3.58 (2H, s), 3.65 (2H, t, J=5.2 Hz), 3.85 (3H, s), 6.94 (2H, d, J=8.8 Hz), 7.44 (2H, d, J=8.3 Hz), 7.59 (1H, m), 7.69-7.80 (3H, m), 7.98 (2H, d, J=7, 8 Hz), 8.28 (1H, s), 8.60 (1H, d, J=9.0 Hz)

Mass spectrometric value (ESI-MS) 594 (M−1)

Compound 323 N-[4-Bromo-2-(3-methoxy-benzylidene-hydrazinocarbonyl)-phenyl]-4-[4-(2-hydroxy-ethyl)-piperazin-1-ylmethyl]-benzamide

The title compound 323 was produced in the same manner as in Example 5.

¹H-NMR (CDCl₃, 400 MHz): δ 2.45-2.65 (10H, m), 3.57 (2H, s), 3.63 (2H, t, J=5.4 Hz), 3.86 (3H, s), 6.98 (1H, m), 7.17 (1H, m), 7.22-7.58 (5H, m), 7.71 (1H, s), 7.97 (2H, d, J=7.8 Hz), 8.38 (1H, s), 8.50 (1H, d, J=8.8 Hz)

Mass spectrometric value (ESI-MS) 592 (M−1)

Compound 324 N-[4-Bromo-2-(3,4-dimethyl-benzylidene-hydrazinocarbonyl)-phenyl]-4-(4-hydroxy-piperidin-1-ylmethyl)-benzamide

The title compound 324 was produced in the same manner as in Example 5.

¹H-NMR (CDCl₃, 400 MHz): δ 1.61 (2H, m), 1.86-2.24 (4H, m), 2.89 (3H, s), 2.30 (3H, s), 2.75 (2H, m), 3.57 (2H, s), 3.71 (1H, m), 7.18 (1H, d, J=7.8 Hz), 7.45 (3H, m), 7.55 (1H, m), 7.64 (1H, s), 7.69 (1H, s), 7.98 (2H, d, J=7.6 Hz), 8.30 (1H, s), 8.54 (1H, d, J=9.0 Hz)

Mass spectrometric value (ESI-MS) 563 (M−1)

Compound 325 N-[4-Bromo-2-(4-methyl-benzylidene-hydrazinocarbonyl)-phenyl]-4-(4-hydroxy-piperidin-1-ylmethyl)-benzamide

The title compound 325 was produced in the same manner as in Example 5.

¹H-NMR (CDCl₃, 400 MHz): δ 1.60 (2H, m), 1.89 (2H, m), 2.17 (2H, m), 2.39 (3H, s), 2.74 (2H, m), 3.56 (2H, m), 3.71 (1H, s), 7.15-7.27 (2H, m), 7.44 (2H, d, J=8.0 Hz), 7.56 (1H, m), 7.69 (3H, m), 7.98 (2H, d, J=8.0 Hz), 8.32 (1H, s), 8.55 (1H, d, J=9.0 Hz)

Mass spectrometric value (ESI-MS) 549 (M−1)

Compound 326 N-[4-Bromo-2-(3-methyl-benzylidene-hydrazinocarbonyl)-phenyl]-4-(4-hydroxy-piperidin-1-ylmethyl)-benzamide

The title compound 326 was produced in the same manner as in Example 5.

¹H-NMR (CDCl₃, 400 MHz): δ 1.60 (2H, m), 1.90 (2H, m), 2.17 (2H, m), 2.40 (3H, s), 2.74 (2H, m), 3.56 (2H, m), 3.71 (1H, m), 7.24-7.34 (2H, m), 7.45 (2H, m), 7.58 (2H, m), 7.70 (2H, m), 7.98 (2H, d, J=7.8 Hz), 8.31 (1H, s), 8.57 (1H, d, J=9.0 Hz)

Mass spectrometric value (ESI-MS) 547 (M−1)

Compound 327 N-[4-Bromo-2-(4-fluoro-benzylidene-hydrazinocarbonyl)-phenyl]-4-(4-hydroxy-piperidin-1-ylmethyl)-benzamide

The title compound 327 was produced in the same manner as in Example 5.

¹H-NMR (CDCl₃, 400 MHz): δ 1.59 (2H, m), 1.89 (2H, m), 2.17 (2H, m), 2.74 (2H, m), 3.56 (2H, s), 3.72 (1H, m), 7.13 (2H, m), 7.45 (2H, d, J=8.0 Hz), 7.56 (1H, m), 7.66 (1H, s), 7.82 (2H, m), 7.98 (2H, d, J=8.0 Hz), 8.36 (1H, s), 8.51 (1H, d, J=8.0 Hz)

Mass spectrometric value (ESI-MS) 551 (M−1)

Compound 328 N-[4-Bromo-2-(3-fluoro-benzylidene-hydrazinocarbonyl)-phenyl]-4-(4-hydroxy-piperidin-1-ylmethyl)-benzamide

The title compound 328 was produced in the same manner as in Example 5.

¹H-NMR (CDCl₃, 400 MHz): δ 1.65 (2H, m), 1.93 (2H, m), 2.30 (2H, m), 2.80 (2H, m), 3.65 (2H, s), 3.75 (1H, m), 7.15 (1H, m), 7.26-7.69 (7H, m), 7.99 (2H, d, J=7.8 Hz), 8.35 (1H, s), 8.54 (1H, d, J=9.0 Hz)

Mass spectrometric value (ESI-MS) 551 (M−1)

Compound 329 N-[4-Bromo-2-(4-chloro-3-trifluoromethyl-benzylidene-hydrazinocarbonyl)-phenyl]-4-(4-hydroxy-piperidin-1-ylmethyl)-benzamide

The title compound 329 was produced in the same manner as in Example 5.

¹H-NMR (CDCl₃, 400 MHz): δ 1.58 (2H, m), 1.91 (2H, m), 2.38 (2H, m), 2.75 (2H, m), 3.58 (2H, s), 3.71 (1H, m), 7.16 (1H, m), 7.47 (2H, d, J=8.1 Hz), 7.52-7.75 (4H, m), 7.98 (2H, d, J=8.1 Hz), 8.24 (1H, s), 8.58 (1H, m)

Mass spectrometric value (ESI-MS) 635 (M−1)

Compound 330 N-[4-Bromo-2-(4-methoxy-benzylidene-hydrazinocarbonyl)-phenyl]-4-(4-hydroxy-piperidin-1-ylmethyl)-benzamide

The title compound 330 was produced in the same manner as in Example 5.

¹H-NMR (CDCl₃, 400 MHz): δ 1.62 (2H, m), 1.90 (2H, m), 2.20 (2H, m), 2.75 (2H, m), 3.59 (2H, s), 3.72 (1H, m), 3.86 (3H, s), 6.95 (2H, d, J=8.8 Hz), 7.45 (2H, d, J=8.0 Hz), 7.62-7.80 (4H, m), 7.98 (2H, m), 8.21 (1H, s), 8.70 (1H, m)

Mass spectrometric value (ESI-MS) 565 (M−1)

Compound 331 N-[4-Bromo-2-(3-methoxy-benzylidene-hydrazinocarbonyl)-phenyl]-4-(4-hydroxy-piperidin-1-ylmethyl)-benzamide

The title compound 331 was produced in the same manner as in Example 5.

¹H-NMR (CDCl₃, 400 MHz): δ 1.60 (2H, m), 1.90 (2H, m), 2.17 (2H, m), 2.75 (2H, m), 2.57 (2H, s), 2.72 (1H, m), 3.87 (3H, s), 6.99 (1H, m), 7.25-7.77 (7H, m), 7.97 (2H, d, J=7.5 Hz), 8.30 (1H, s), 8.63 (1H, d, J=8.6 Hz)

Mass spectrometric value (ESI-MS) 563 (M−1)

Compound 332 N-[4-Bromo-2-(3,4-dimethyl-benzylidene-hydrazinocarbonyl)-phenyl]-4-(4-hydroxymethyl-piperidin-1-ylmethyl)-benzamide

The title compound 332 was produced in the same manner as in Example 5.

¹H-NMR (CDCl₃, 400 MHz): δ 1.25-1.76 (5H, m), 2.03 (2H, m), 2.28 (3H, s), 2.29 (3H, s), 2.91 (2H, m), 3.50 (2H, d, J=6.3 Hz), 3.58 (2H, s), 7.17 (1H, m), 7.41-7.72 (6H, m), 7.98 (2H, d, J=8.0 Hz), 8.32 (1H, s), 8.53 (1H, d, J=8.5 Hz)

Mass spectrometric value (ESI-MS) 575 (M−1)

Compound 333 N-[4-Bromo-2-(4-methyl-benzylidene-hydrazinocarbonyl)-phenyl]-4-(4-hydroxymethyl-piperidin-1-ylmethyl)-benzamide

The title compound 333 was produced in the same manner as in Example 5.

¹H-NMR (CDCl₃, 400 MHz): δ 1.20-1.76 (5H, m), 2.04 (2H, m), 2.39 (3H, s), 2.93 (2H, m), 3.50 (2H, d, J=6.4 Hz), 3.60 (2H, s), 7.24 (2H, m), 7.42-7.76 (6H, m), 7.98 (2H, d, J=7.8 Hz), 8.33 (1H, s), 8.58 (1H, d, J=8.8 Hz)

Mass spectrometric value (ESI-MS) 561 (M−1)

Compound 334 N-[4-Bromo-2-(3-methyl-benzylidene-hydrazinocarbonyl)-phenyl]-4-(4-hydroxymethyl-piperidin-1-ylmethyl)-benzamide

The title compound 334 was produced in the same manner as in Example 5.

¹H-NMR (CDCl₃, 400 MHz): δ 1.20-2.15 (7H, m), 2.38 (3H, s), 2.93 (2H, m), 3.40-3.65 (4H, m), 7.20-7.32 (1H, m), 7.40-7.70 (6H, m), 8.27 (1H, s), 8.65 (1H, d, J=8.8 Hz)

Mass spectrometric value (ESI-MS) 563 (M−1)

Compound 335 N-[4-Bromo-2-(4-fluoro-benzylidene-hydrazinocarbonyl)-phenyl]-4-(4-hydroxymethyl-piperidin-1-ylmethyl)-benzamide

The title compound 335 was produced in the same manner as in Example 5.

¹H-NMR (CDCl₃, 400 MHz): δ 1.20-1.40 (5H, m), 1.72 (2H, m), 2.93 (2H, m), 3.47-3.65 (4H, m), 7.12 (2H, m), 7.40-7.88 (6H, m), 7.98 (2H, d, J=8.5 Hz), 8.47 (1H, s), 8.54 (1H, d, J=8.8 Hz)

Mass spectrometric value (ESI-MS) 567 (M−1)

Compound 336 N-[4-Bromo-2-(3-fluoro-benzylidene-hydrazinocarbonyl)-phenyl]-4-(4-hydroxymethyl-piperidin-1-ylmethyl)-benzamide

The title compound 336 was produced in the same manner as in Example 5.

¹H-NMR (CDCl₃, 400 MHz): δ 1.20-1.80 (5H, m), 2.05 (2H, m), 2.93 (2H, m), 3.42-3.65 (4H, m), 7.12 (1H, m), 7.24-7.66 (6H, m), 7.82 (1H, s), 7.97 (2H, d, J=8.3 Hz), 8.30 (1H, s), 8.64 (1H, d, J=9.0 Hz)

Mass spectrometric value (ESI-MS) 565 (M−1)

Compound 337 N-[4-Bromo-2-(4-chloro-3-trifluoromethyl-benzylidene-hydrazinocarbonyl)-phenyl]-4-(4-hydroxymethyl-piperidin-1-ylmethyl)-benzamide

The title compound 337 was produced in the same manner as in Example 5.

¹H-NMR (CDCl₃, 400 MHz): δ 1.20-2.22 (7H, m), 2.92 (2H, m), 3.39-3.65 (4H, m), 7.14-8.10 (9H, m), 8.32 (1H, s), 8.64 (1H, d, J=8.8 Hz)

Mass spectrometric value (ESI-MS) 649 (M−1)

Compound 338 N-[4-Bromo-2-(4-methoxy-benzylidene-hydrazinocarbonyl)-phenyl]-4-(4-hydroxymethyl-piperidin-1-ylmethyl)-benzamide

The title compound 338 was produced in the same manner as in Example 5.

¹H-NMR (CDCl₃, 400 MHz): δ 1.20-1.76 (5H, m), 2.03 (2H, m), 2.91 (2H, m), 3.46-3.64 (4H, m), 3.84 (3H, s), 6.93 (2H, m), 7.41-7.80 (6H, m), 7.97 (2H, d, J=7.8 Hz), 8.32 (1H, s), 8.55 (1H, d, J=9.0 Hz)

Mass spectrometric value (ESI-MS) 579 (M−1)

Compound 339 N-[4-Bromo-2-(3-methoxy-benzylidene-hydrazinocarbonyl)-phenyl]-4-(4-hydroxymethyl-piperidin-1-ylmethyl)-benzamide

The title compound 339 was produced in the same manner as in Example 5.

¹H-NMR (CDCl₃, 400 MHz): δ 1.20-2.25 (7H, m), 2.95 (2H, m), 3.45-3.67 (4H, m), 3.87 (3H, s), 6.80-7.80 (8H, m), 7.95 (2H, m), 8.25 (1H, s), 8.65 (1H, m)

Mass spectrometric value (ESI-MS) 577 (M−1)

Compound 340 N-[4-Bromo-2-(3,4-dimethyl-benzylidene-hydrazinocarbonyl)-phenyl]-4-[4-(2-hydroxy-ethyl)-piperidin-1-ylmethyl]-benzamide

The title compound 340 was produced in the same manner as in Example 5.

¹H-NMR (DMSO-d₆, 400 MHz): δ 1.15 (2H, m), 1.35 (3H, m), 1.61 (2H, m), 1.92 (2H, m), 2.27 (3H, s), 2.29 (3H, s), 2.77 (2H, m), 3.42 (2H, m), 3.52 (2H, s), 7.24 (1H, d, J=7.8 Hz), 7.48 (3H, m), 7.55 (1H, s), 7.80 (1H, dd, J=9.0 Hz, J=2.4 Hz), 7.88 (2H, d, J=8.0 Hz), 8.09 (1H, d, J=2.4 Hz), 8.38 (1H, s), 8.52 (1H, d, J=9.0 Hz)

Mass spectrometric value (ESI-MS) 589 (M−1)

Example 6 Compound 341 N-[4-Bromo-2-(3-fluoro-benzylidene-hydrazinocarbonyl)-phenyl]-3-(1H-[1,2,4]triazole-3-sulfinylmethyl)-benzamide Compound 271: N-[4-bromo-2-(3-fluoro-benzylidene-hydrazinocarbonyl)-phenyl]-3-(1H-[1,2,4]triazol-3-ylsulfanylmethyl)-benzamide (100 mg) produced in the same manner as in Example 5 was dissolved in methylene chloride (5 ml), 3-chloro-peroxybenzoic acid (32 mg) was added to the solution, and the mixture was stirred at room temperature for 2 hr. The resultant crystals were filtered and were washed with methylene chloride and hexane to give the title compound 341 (76 mg, yield 70%).

¹H-NMR (DMSO-d₆, 400 MHz): δ 4.65 (2H, m), 7.29 (1H, m), 7.53 (4H, m), 7.83 (3H, m), 8.08 (1H, d, J=2.0 Hz), 8.43 (2H, m), 8.83 (1H, s), 11.72 (1H, s)

Mass spectrometric value (ESI-MS) 569 (M−1)

Compound 342 3-{[(2-Diethylamino-ethyl)-methyl-amino]-methyl}-N-[2-(3,4-dimethyl-benzylidene-hydrazinocarbonyl)-4-methyl-thiophen-3-yl]-benzamide

The title compound 342 was produced in the same manner as in Example 5.

¹H-NMR (CDCl₃, 400 MHz): δ 1.07 (6H, m), 2.30 (12H, m), 2.56 (8H, m), 3.61 (2H, s), 7.18 (1H, d, J=7.6 Hz), 7.30-7.60 (6H, m), 7.93 (1H, d, J=7.6 Hz), 8.01 (1H, s)

Mass spectrometric value (ESI-MS) 532 (M−1)

Compound 343 3-{[(2-Diethylamino-ethyl)-methyl-amino]-methyl}-N-[4-methyl-2-(4-methyl-benzylidene-hydrazinocarbonyl)-thiophen-3-yl]-benzamide

The title compound 343 was produced in the same manner as in Example 5.

¹H-NMR (CDCl₃, 400 MHz): δ 1.05 (6H, t, J=7.1 Hz), 2.26 (3H, s), 2.31 (3H, s), 2.39 (3H, s), 2.51-2.80 (8H, m), 3.60 (2H, s), 7.21 (2H, d, J=7.6 Hz), 7.30-7.80 (6H, m), 7.93 (1H, d, J=7.6 Hz), 8.00 (1H, s)

Mass spectrometric value (ESI-MS) 518 (M−1)

Compound 344 N-[2-(4-Chloro-3-trifluoromethyl-benzylidene-hydrazinocarbonyl)-4-methyl-thiophen-3-yl]-3-{[(2-diethylamino-ethyl)-methyl-amino]-methyl}-benzamide

The title compound 344 was produced in the same manner as in Example 5.

¹H-NMR (CDCl₃, 400 MHz): δ 1.03 (6H, t, J=7.2 Hz), 2.25 (3H, s), 2.27 (3H, s), 2.52-2.70 (8H, m), 3.60 (2H, s), 7.35-7.60 (5H, m), 7.80 (1H, m), 7.92 (1H, d, J=7.6 Hz), 8.00 (2H, d, J=3.9 Hz)

Mass spectrometric value (ESI-MS) 606 (M−1)

Compound 345 3-[1,4′]Bipiperidinyl-1′-ylmethyl-N-[2-(3,4-dimethyl-benzylidene-hydrazinocarbonyl)-4-methyl-thiophen-3-yl]-benzamide

The title compound 345 was produced in the same manner as in Example 5.

¹H-NMR (CDCl₃, 400 MHz): δ 1.44 (2H, m), 1.50-2.10 (12H, m), 2.30 (10H, m), 2.57 (2H, m), 2.96 (2H, d, J=11.7 Hz), 3.56 (2H, s), 7.17 (1H, d, J=7.6 Hz), 7.30-7.55 (6H, m), 7.92 (1H, d, J=7.6 Hz), 7.99 (1H, s)

Mass spectrometric value (ESI-MS) 570 (M−1)

Compound 346 N-[4-Bromo-2-(3-phenyl-allylidene-hydrazinocarbonyl)-phenyl]-nicotinamide

The title compound 346 was produced in the same manner as in Example 1.

¹H-NMR (CD₃OD, 400 MHz): δ 9.15 (1H, s), 8.73-8.78 (1H, m), 8.54 (1H, d, J=8.8 Hz), 8.26-8.42 (1H, m), 8.17 (1H, d, J=6.6 Hz), 8.06 (1H, d, J=2.2 Hz), 7.77 (1H, dd, J=8.8 Hz, J=2.2 Hz), 7.55-7.64 (3H, m), 7.30-7.42 (3H, m), 7.05-7.10 (2H, m)

Mass spectrometric value (ESI-MS) 447 (M−1)

Compound 347 N-[4-Bromo-2-(3-phenyl-allylidene-hydrazinocarbonyl)-phenyl]-isonicotinamide

The title compound 347 was produced in the same manner as in Example 1.

¹H-NMR (CD₃OD, 400 MHz): δ 8.75-8.00 (2H, m), 8.57 (1H, d, J=9.0 Hz), 8.28 (1H, d, J=7.3 Hz), 8.05-8.08 (1H, m), 7.92-7.95 (2H, m), 7.78 (1H, dd, J=2.4 Hz, J=9.0 Hz), 7.57 (2H, d, J=7.8 Hz), 7.30-7.42 (3, m), 7.05-7.10 (2H, m)

Mass spectrometric value (ESI-MS) 447 (M−1)

Compound 348 N-[4-Chloro-2-(3-phenyl-allylidene-hydrazinocarbonyl)-phenyl]-nicotinamide

The title compound 348 was produced in the same manner as in Example 1.

¹H-NMR (CD₃OD, 400 MHz): δ 9.14-9.18 (1H, m), 8.75 (1H, dd, J=4.9 Hz, J=1.5 Hz), 8.59 (1H, d, J=8.8 Hz), 8.39 (1H, ddd, J=1.4 Hz, J=1.4 Hz, J=8.0 Hz), 8.17 (1H, d. J=6.8 Hz), 7.92 (1H, d, J=2.4 Hz), 7.55-7.65 (4H, m), 7.30-7.42 (3H, m), 7.05-7.10 (2H, m)

Mass spectrometric value (ESI-MS) 403 (M−1)

Compound 349 N-[4-Chloro-2-(3-phenyl-allylidene-hydrazinocarbonyl)-phenyl]-isonicotinamide

The title compound 349 was produced in the same manner as in Example 1.

¹H-NMR (CD₃OD, 400 MHz): δ 8.78 (2H, dd, J=1.7 Hz, J=4.4 Hz), 8.62 (1H, d, J=9.0 Hz), 8.18 (1H, dd, J=1.4 Hz, J=7.6 Hz), 7.93-7.97 (3H, m), 7.64 (1H, dd, J=2.2 Hz, J=9.0 Hz), 7.55-7.60 (2H, m), 7.31-7.43 (3H, m), 7.06-7.12 (2H, m)

Mass spectrometric value (ESI-MS) 403 (M−1)

Compound 350 N-{4-Bromo-2-[3-(2-hydroxy-ethoxy)-benzylidene-hydrazinocarbonyl]-phenyl}-isonicotinamide

The title compound 350 was produced in the same manner as in Example 1.

¹H-NMR (CD₃OD, 400 MHz): δ 8.78 (2H, dd, J=1.7 Hz, J=4.4 Hz), 8.57 (1H, d, J=8.8 Hz), 8.31 (1H, s), 8.08 (1H, d, J=2.2 Hz), 7.95 (2H, dd, J=1.7 Hz, J=4.6 Hz), 7.81 (1H, s), 7.77-7.79 (1H, m), 7.76 (1H, d, J=2.2 Hz), 7.03 (2H, d, J=8.8 Hz), 4.11 (2H, t, J=9.5 Hz), 3.89 (2H, t, J=9.3 Hz)

Mass spectrometric value (ESI-MS) 481 (M−1)

Compound 351 N-{4-Chloro-2-[3-(2-hydroxy-ethoxy)-benzylidene-hydrazinocarbonyl]-phenyl}-isonicotinamide

The title compound 351 was produced in the same manner as in Example 1.

¹H-NMR (CD₃OD, 400 MHz): δ 8.78 (2H, dd, J=1.7 Hz, J=4.6 Hz), 8.63 (1H, d, J=9.0 Hz), 8.31 (1H, s), 7.93-7.97 (3H, m), 7.79 (2H, d, J=8.8 Hz), 7.64 (1H, dd, J=2.4 Hz, J=9.0 Hz), 7.03 (2H, d, J=8.8 Hz), 4.11 (2H, t, J=4.8 Hz), 3.89 (2H, t, J=4.8 Hz)

Mass spectrometric value (ESI-MS) 437 (M−1)

Compound 352 N-{4-Bromo-2-[3-(2-methoxy-phenyl)-allylidene-hydrazinocarbonyl]-phenyl}-nicotinamide

The title compound 352 was produced in the same manner as in Example 1.

¹H-NMR (CD₃OD, 400 MHz): δ 9.15 (1H, d, J=2.2 Hz), 8.75 (1H, dd, J=1.4 Hz, J=4.9 Hz), 8.39 (1H, ddd, J=1.8 Hz, J=1.8 Hz, J=7.8 Hz), 8.16 (1H, d, J=9.2 Hz), 8.06 (1H, d, J=2.4 Hz), 7.77 (1H, dd, J=2.4 Hz, J=9.0 Hz), 7.56-7.65 (2H, m), 7.30-7.40 (2H, m), 7.11 (1H, dd, J=9.5 Hz, J=6.1 Hz), 7.02 (1H, d, J=8.3 Hz), 6.97 (1H, dd, J=7.7 Hz), 3.90 (3H, s)

Mass spectrometric value (ESI-MS) 479, 480 (M−1)

Compound 353 N-{4-Bromo-2-[3-(2-methoxy-phenyl)-allylidene-hydrazinocarbonyl]-phenyl}-isonicotinamide

The title compound 353 was produced in the same manner as in Example 1.

¹H-NMR (CD₃OD, 400 MHz): δ 8.76-8.80 (2H, m), 8.57 (1H, d, J=8.8 Hz), 8.17 (1H, d, J=9.5 Hz), 8.07 (1H, d, J=2.4 Hz), 7.94 (2H, dd, J=1.7 Hz, J=4.4 Hz), 7.78 (1H, dd, J=2.4 Hz, J=8.9 Hz), 7.59 (1H, d, J=6.4 Hz), 7.30-7.41 (2H, m), 6.95-7.24 (3H, m), 3.90 (3H, s)

Mass spectrometric value (ESI-MS) 479, 480 (M−1)

Compound 354 N-{4-Chloro-2,3-(2-methoxy-phenyl)-allylidene-hydrazinocarbonyl]-phenyl}-nicotinamide

The title compound 354 was produced in the same manner as in Example 1.

¹H-NMR (CD₃OD, 400 MHz): δ 9.16 (1H, d, J=2.4 Hz), 8.76 (1H, dd, J=2.1 Hz, J=5.3 Hz), 8.60 (1H, d, J=9.0 Hz), 8.35-8.42 (1H, m), 8.16 (1H, d, J=9.5 Hz), 7.92 (1H, d, J=2.4 Hz), 7.58-7.65 (3H, m), 7.30-7.41 (2H, m), 7.11 (1H, dd, J=9.5 Hz, J=16.1 Hz), 7.02 (1H, d, J=7.8 Hz), 6.97 (1H, dd, J=7.6 Hz, J=7.6 Hz), 3.90 (3H, s)

Mass spectrometric value (ESI-MS) 433 (M−1)

Compound 355 N-{4-Chloro-2-[3-(2-methoxy-phenyl)-allylidene-hydrazinocarbonyl]-phenyl}-isonicotinamide

The title compound 355 was produced in the same manner as in Example 1.

¹H-NMR (CD₃OD, 400 MHz): δ 8.78 (2H, d, J=4.4 Hz), 8.63 (1H, d, J=8.8 Hz), 8.17 (1H, d, J=9.3 Hz), 7.92-7.98 (3H, m), 7.55-7.70 (2H, m), 7.30-7.38 (2H, m), 7.07-7.17 (1H, m), 6.95-7.05 (2H, m)

Mass spectrometric value (ESI-MS) 435 (M−1)

Compound 356 Pyridin-2-carboxylic acid [4-bromo-2-(4-methyl-benzylidene-hydrazinocarbonyl)-phenyl]-amide hydrochloride

The title compound 356 was produced in the same manner as in Example 3.

Mass spectrometric value (ESI-MS) 473 (M−1)

Compound 357 N-[4-Bromo-2-(3-methyl-benzylidene-hydrazinocarbonyl)-phenyl]-4-(3-fluoro-phenylsulfanylmethyl)-benzamide

The title compound 357 was produced in the same manner as in Example 4.

¹H-NMR (CD₃OD, 400 MHz): δ 8.59 (1H, d, J=8.8 Hz), 8.33 (1H, s), 8.05-8.08 (1H, m), 7.93 (2H, d, J=8.6 Hz), 7.60-7.80 (4H, m), 7.51 (2H, d, J=8.6 Hz), 6.80-7.40 (5H, m), 4.27 (2H, s), 2.40 (3H, s)

Mass spectrometric value (ESI-MS) 574 (M−1)

Compound 358 N-{2-[3-(4-Dimethylamino-phenyl)-allylidene-hydrazinocarbonyl]-phenyl}-nicotinamide

The title compound 358 was produced in the same manner as in Example 1.

¹H-NMR (CD₃OD, 400 MHz): δ 9.17 (1H, s, J=1.5 Hz), 8.75 (1H, dd, J=1.5 Hz, H=4.9 Hz), 8.60 (1H, d, J=8.3 Hz), 8.38-8.44 (1H, m), 8.11 (1H, d, J=9.0 Hz), 7.85 (1H, d, J=7.8 Hz), 7.60-7.65 (2H, m), 7.42 (2H, d, J=8.8 Hz), 7.29 (1H, dd, J=7.7 Hz, J=7.7 Hz), 6.94-7.00 (1H, m), 6.80-6.88 (1H, m), 6.74 (2H, d, J=9.0 Hz), 3.00 (6H, s)

Mass spectrometric value (ESI-MS) 412 (M−1)

Compound 359 Pyridin-2-carboxylic acid [4-chloro-2-(3-fluoro-benzylidene-hydrazinocarbonyl)-phenyl]-amide

The title compound 359 was produced in the same manner as in Example 1.

¹H-NMR (CD₃OD, 400 MHz): δ 8.79 (1H, d, J=9.0 Hz), 8.73 (1H, d, J=5.1 Hz), 8.33 (1H, s), 8.22 (1H, d, J=7.8 Hz), 7.98-8.04 (1H, m), 7.89 (1H, d, J=2.4 Hz), 7.73 (1H, d, J=10.0 Hz), 7.58-7.66 (3H, m), 7.42-7.50 (1H, m), 7.15-7.22 (1H, m)

Mass spectrometric value (ESI-MS) 395 (M−1)

Compound 360 Pyridin-2-carboxylic acid [4-chloro-2-(4-fluoro-benzylidene-hydrazinocarbonyl)-phenyl]-amide

The title compound 360 was produced in the same manner as in Example 1.

¹H-NMR (CD₃OD, 400 MHz): δ 8.78 (1H, d, J=8.8 Hz), 8.72 (1H, d, J=4.9 Hz), 8.33 (1H, s), 8.22 (1H, d, J=7.8 Hz), 8.01 (1H, ddd, J=7.8 Hz, J=7.8 Hz, J=1.4 Hz), 7.89-7.95 (2H, m), 7.88 (1H, d, J=2.4 Hz), 7.58-7.65 (2H, m), 7.19 (2H, dd, J=8.8 Hz, J=8.8 Hz)

Mass spectrometric value (ESI-MS) 395 (M−1)

Compound 361 Pyridin-2-carboxylic acid [4-chloro-2-(3-methyl-benzylidene-hydrazinocarbonyl)-phenyl]-amide

The title compound 361 was produced in the same manner as in Example 1.

¹H-NMR (CD₃OD, 400 MHz): δ 8.78 (1H, d, J=9.0 Hz), 8.73 (1H, d, J=4.6 Hz), 8.31 (1H, s), 8.22 (1H, d, J=7.8 Hz), 7.98-8.04 (1H, m), 7.88 (1H, d, J=2.4 Hz), 7.72 (1H, s), 7.56-7.66 (3H, m), 7.24-7.35 (2H, m), 2.40 (3H, s)

Mass spectrometric value (ESI-MS) 391 (M−1)

Compound 362 Pyridin-2-carboxylic acid [4-chloro-2-(4-methyl-benzylidene-hydrazinocarbonyl)-phenyl]-amide

The title compound 362 was produced in the same manner as in Example 1.

¹H-NMR (CD₃OD, 400 MHz): δ 8.78 (1H, d, J=8.8 Hz), 8.73 (1H, d, J=4.9 Hz), 8.30 (1H, s), 8.22 (1H, d, J=7.8 Hz), 8.01 (1H, ddd, J=8.5 Hz, J=8.5 Hz, J=1.7 Hz), 7.87 (1H, d, J=2.4 Hz), 7.75 (2H, d, J=8.0 Hz), 7.57-7.64 (2H, m), 7.27 (2H, d, J=8.0 Hz), 2.38 (3H, s)

Mass spectrometric value (ESI-MS) 391 (M−1)

Compound 363 Pyridin-2-carboxylic acid [4-chloro-2-(3,4-dimethyl-benzylidene-hydrazinocarbonyl)-phenyl]-amide

The title compound 363 was produced in the same manner as in Example 1.

¹H-NMR (CD₃OD, 400 MHz): δ 8.77 (1H, d, J=9.0 Hz), 8.73 (1H, d, J=4.4 Hz), 8.27 (1H, s), 8.22 (1H, d, J=7.8 Hz), 8.00 (1H, ddd, J=1.7 Hz, J=7.7 Hz, J=7.7 Hz), 7.87 (1H, d, J=2.4 Hz), 7.67 (1H, s), 7.53-7.64 (3H, m), 7.20 (1H, d, J=7.8 Hz), 2.32 (3H, s), 2.30 (3H, s)

Mass spectrometric value (ESI-MS) 405 (M−1)

Compound 364 Pyridin-2-carboxylic acid [4-chloro-2-(4-chloro-3-trifluoromethyl-benzylidene-hydrazinocarbonyl)-phenyl]amide

The title compound 364 was produced in the same manner as in Example 1.

¹H-NMR (CD₃OD, 400 MHz): δ 8.79 (1H, d, J=9.0 Hz), 8.71-8.75 (1H, m), 8.35-8.40 (2H, m), 8.22 (1H, d, J=7.8 Hz), 8.07 (1H, d, J=8.3 Hz), 7.98-8.04 (1H, m), 7.90 (1H, d, J=2.2 Hz), 7.70 (1H, d, J=8.6 Hz), 7.58-7.67 (2H, m)

Mass spectrometric value (ESI-MS) 479 (M−1)

Compound 366 N-{4-Chloro-2-[N′-(3,4-dimethyl-benzyl)-hydrazinocarbonyl]-phenyl}-3-(pyridin-4-ylsulfanylmethyl)-benzamide

The title compound 366 was produced in the same manner as in Example 7.

Mass spectrometric value (ESI-MS) 529, 531, 532 (M−1)

Example 7 Compound 367 N-{4-Bromo-2-[N′-(4-methyl-benzyl)-hydrazinocarbonyl]-phenyl}-3,4-dimethoxy-benzamide

Compound 62: N-[4-bromo-2-(4-methyl-benzylidene-hydrazinocarbonyl)-phenyl]-3,4-dimethoxy-benzamide (100 mg) produced in the same manner as in Example 1 was dissolved in a mixed solution (2.0 ml) of tetrahydrofuran/methanol=4/1, and sodium borohydride (14.0 mg) was added to the mixed solution at room temperature. The mixture was stirred at that temperature for 30 min, and, after the completion of the reaction was confirmed by TLC, distilled water (2.0 ml) was poured thereinto. The mixture was subjected to separatory extraction with chloroform, and the organic layer was dried over sodium sulfate and was then concentrated under the reduced pressure. The residue was purified by preparative TLC to give the title compound 367 (42.2 mg).

¹H-NMR (CD₃OD, 400 MHz): δ 8.66 (1H, d, J=8.8 Hz), 8.35 (1H, s), 8.06 (1H, s), 7.87-7.95 (4H, m), 7.63 (1H, d, J=8.8 Hz), 7.62 (1H, d, J=8.8 Hz), 7.50 (1H, dd, J=7.6 Hz, J=7.6 Hz), 7.19 (2H, dd, J=8.8 Hz), 3.83 (2H, s), 3.65 (4H, t, J=5.9 Hz), 2.71 (4H, t, J=5.9 Hz)

Mass spectrometric value (ESI-MS) 496, 497, 498, 499 (M−1)

Compound 368 3-[1,4′]Bipiperidinyl-1′-ylmethyl-N-[4-chloro-2-(3-fluoro-benzylidene-hydrazinocarbonyl)-phenyl]-benzamide

The title compound 368 was produced in the same manner as in Example 5.

¹H-NMR (CD₃OD, 400 MHz): δ 8.64 (1H, d, J=8.8 Hz), 8.35 (1H, s), 7.89-7.98 (3H, m), 7.70 (1H, d, J=9.8 Hz), 7.57-7.64 (3H, m), 7.42-7.50 (2H, m), 7.10-7.23 (1H, m), 3.62 (2H, s), 2.99 (2H, d, J=12.0 Hz), 2.59 (4H, bs), 2.29-2.39 (1H, m), 2.06 (2H, t, J=11.5 Hz), 1.86 (2H, d, J=11.7 Hz), 1.55-1.68 (6H, m), 1.40-1.50 (2H, m)

Mass spectrometric value (ESI-MS) 574, 576 (M−1)

Compound 369 3-[1,4′]Bipiperidinyl-t-ylmethyl-N-[4-chloro-2-(4-fluoro-benzylidene-hydrazinocarbonyl)-phenyl]-benzamide

The title compound 369 was produced in the same manner as in Example 5.

¹H-NMR (CD₃OD, 400 MHz): δ 8.63 (1H, d, J=9.0 Hz), 8.35 (1H, s), 7.88-7.97 (5H, m), 7.56-7.64 (2H, m), 7.52 (1H, dd, J=7.7 Hz, J=7.7 Hz), 7.15-7.22 (2H, m), 3.62 (2H, s), 3.98 (2H, d, J=12.2 Hz), 2.57 (4H, bs), 2.25-2.35 (1H, m), 2.05 (2H, t, J=11.1 Hz), 1.80-1.90 (2H, m), 1.53-1.66 (7H, m), 1.40-1.50 (2H, m)

Mass spectrometric value (ESI-MS) 574, 576 (M−1)

Compound 370 3-[1,4′]Bipiperidinyl-1′-ylmethyl-N-[4-chloro-2-(3-methyl-benzylidene-hydrazinocarbonyl)-phenyl]-benzamide

The title compound 370 was produced in the same manner as in Example 5.

¹H-NMR (CD₃OD, 400 MHz): δ 8.53 (1H, d, J=9.0 Hz), 8.33 (1H, s), 7.88-7.98 (4H, m), 7.71 (1H, s), 7.57-7.65 (3H, m), 7.52 (1H, dd, J=7.7 Hz, J=7.7 Hz), 7.25-7.37 (2H, m), 3.63 (2H, s), 3.99 (2H, d, J=12.0 Hz), 2.56 (4H, bs), 2.39 (3H, s), 2.25-2.37 (1H, m), 2.06 (2H, t, J=11.3 Hz), 1.80-1.90 (2H, m), 1.55-1.64 (6H, m), 1.40-1.49 (2H, m)

Mass spectrometric value (ESI-MS) 570, 571 (M−1)

Compound 371 3-[1,4′]Bipiperidinyl-1′-ylmethyl-N-[4-chloro-2-(4-methyl-benzylidene-hydrazinocarbonyl)-phenyl]-benzamide

The title compound 371 was produced in the same manner as in Example 5.

¹H-NMR (CD₃OD, 400 MHz): δ 8.64 (1H, d, J=9.0 Hz), 8.33 (1H, s), 7.89-7.98 (3H, m), 7.74 (2H, d, J=8.3 Hz), 7.57-7.64 (2H, m), 7.52 (1H, dd, J=7.7 Hz, J=7.7 Hz), 7.27 (2H, d, J=7.8 Hz), 3.63 (2H, s), 2.95-3.05 (2H, m), 2.56 (4H, bs), 2.39 (3H, s), 2.25-2.35 (1H, m), 2.00-2.10 (2H, m), 1.80-1.90 (2H, m), 1.59 (6H, bs), 1.40-1.50 (2H, m)

Mass spectrometric value (ESI-MS) 570, 571 (M−1)

Compound 372 3-[1,4′]Bipiperidinyl-1′-ylmethyl-N-[4-chloro-2-(3,4-dimethyl-benzylidene-hydrazinocarbonyl)-phenyl]-benzamide

The title compound 372 was produced in the same manner as in Example 5.

¹H-NMR (CD₃OD, 400 MHz): δ 8.64 (1H, d, J=9.0 Hz), 8.30 (1H, s), 7.96 (1H, s), 7.89-7.95 (2H, m), 7.65 (1H, s), 7.49-7.68 (4H, m), 7.20 (1H, d, J=8.0 Hz), 3.62 (2H, s), 2.99 (2H, d, J=11.5 Hz), 2.55 (4H, bs), 2.32 (3H, s), 2.30 (3H, s), 2.25-2.30 (1H, m), 2.01-2.10 (2H, m), 1.80-1.88 (2H, m), 1.54-1.65 (6H, m), 1.40-1.50 (2H, m)

Mass spectrometric value (ESI-MS) 584, 585 (M−1)

Compound 373 3-[1,4′]Bipiperidinyl-1-ylmethyl-N-[4-chloro-2-(4-chloro-3-trifluoromethyl-benzylidene-hydrazinocarbonyl)-phenyl]-benzamide

The title compound 373 was produced in the same manner as in Example 5.

¹H-NMR (CD₃OD, 400 MHz): δ 8.63 (1H, d, J=9.0 Hz), 8.35 (1H, s), 8.05 (1H, d, J=8.3 Hz), 7.89-7.98 (4H, m), 7.71 (1H, d, J=8.6 Hz), 7.64 (1H, dd, J=9.0 Hz, J=2.2 Hz), 7.56-7.62 (1H, m), 7.53 (1H, dd, J=7.6 Hz, J=7.6 Hz), 3.66 (2H, s), 3.00-3.10 (6H, m), 2.09-2.18 (3H, m), 1.96-2.03 (2H, m), 1.70-1.80 (6H, m), 1.55-1.65 (2H, m)

Mass spectrometric value (ESI-MS) 658, 660 (M−1)

Compound 374 3-[1,4′]Bipiperidinyl-1′-ylmethyl-N-[4-chloro-2-(3-methoxy-benzylidene-hydrazinocarbonyl)-phenyl]-benzamide

The title compound 374 was produced in the same manner as in Example 5.

¹H-NMR (CD₃OD, 400 MHz): δ 8.62 (1H, d, J=9.0 Hz), 8.32 (1H, s), 7.87-7.98 (4H, m), 7.47-7.65 (4H, m), 7.28-7.38 (2H, m), 6.97-7.03 (1H, m), 3.86 (3H, s), 3.61 (3H, s), 2.97 (2H, d, J=10.5 Hz), 2.55 (4H, bs), 2.25-2.35 (1H, m), 1.97-2.10 (2H, m), 1.80-1.88 (2H, m), 1.54-1.65 (6H, m), 1.44 (2H, bs)

Mass spectrometric value (ESI-MS) 586, 588 (M−1)

Compound 375 3-[1,4′]Bipiperidinyl-1′-ylmethyl-N-[4-chloro-2-(4-methoxy-benzylidene-hydrazinocarbonyl)-phenyl]-benzamide

The title compound 375 was produced in the same manner as in Example 5.

¹H-NMR (CD₃OD, 400 MHz): δ 8.64 (1H, d, J=9.0 Hz), 8.30 (1H, s), 7.96 (1H, s), 7.89-7.94 (2H, m), 7.79 (2H, d, J=8.8 Hz), 7.57-7.64 (2H, m), 7.52 (1H, dd, J=7.6 Hz, J=7.6 Hz), 6.99 (2H, d, J=8.8 Hz), 3.85 (3H, s), 3.62 (2H, s), 3.99 (2H, d, J=12.0 Hz), 2.56 (4H, bs), 2.25-2.35 (1H, m), 2.05 (2H, t, J=11.0 Hz), 1.80-1.90 (2H, m), 1.55-1.65 (6H, m), 1.40-1.50 (2H, m)

Mass spectrometric value (ESI-MS) 586, 587 (M−1)

Compound 376 3-[1,4′]Bipiperidinyl-1′-ylmethyl-N-[4-chloro-2-(3-hydroxy-benzylidene-hydrazinocarbonyl)-phenyl]-benzamide

The title compound 376 was produced in the same manner as in Example 5.

¹H-NMR (CD₃OD, 400 MHz): δ 8.64 (1H, d, J=9.0 Hz), 8.29 (1H, s), 7.89-7.98 (4H, m), 7.62 (1H, dd, J=2.4 Hz, J=9.0 Hz), 7.59 (1H, d, J=7.8 Hz), 7.52 (1H, dd, J=7.6 Hz, J=7.6 Hz), 7.32 (1H, s), 7.20-7.30 (2H, m), 6.85-6.90 (1H, m), 3.64 (2H, s), 3.02 (2H, d, J=11.7 Hz), 2.66 (4H, bs), 2.32 (1H, bs), 2.08 (2H, t, J=11.4 Hz), 1.85-1.93 (2H, m), 1.52-1.68 (6H, m), 1.40-1.51 (2H, m)

Mass spectrometric value (ESI-MS) 572, 574 (M−1)

Compound 377 3-[1,4′]Bipiperidinyl-t-ylmethyl-N-[4-chloro-2-(4-hydroxy-benzylidene-hydrazinocarbonyl)-phenyl]-benzamide

The title compound 377 was produced in the same manner as in Example 5.

¹H-NMR (CD₃OD, 400 MHz): δ 8.64 (1H, d, J=9.0 Hz), 8.26 (1H, s), 7.96 (1H, s), 7.88-7.94 (2H, m), 7.70 (1H, d, J=8.8 Hz), 7.62 (2H, d, J=2.4 Hz), 7.57-7.63 (2H, m), 7.52 (1H, dd, J=7.6 Hz, J=7.6 Hz), 6.84 (2H, d, J=8.5 Hz), 3.63 (2H, s), 2.99 (2H, d, J=12.0 Hz), 2.57 (4H, bs), 2.27-2.36 (1H, m), 2.06 (2H, t, J=11.2 Hz), 1.85 (2H, d, J=12.7 Hz), 1.52-1.67 (6H, m), 1.40-1.50 (2H, m)

Mass spectrometric value (ESI-MS) 572, 574, 575 (M−1)

Compound 378 4-[1,4′]Bipiperidinyl-1′-ylmethyl-N-{4-bromo-2-[N′-(3-methoxy-benzyl)-hydrazinocarbonyl]-phenyl}-benzamide

The title compound 378 was produced in the same manner as in Example 7.

Mass spectrometric value (ESI-MS) 632, 634 (M−1)

Compound 379 N-[4-Chloro-2-(3-fluoro-benzylidene-hydrazinocarbonyl)-phenyl]-3-{[(2-diethylamino-ethyl)-methyl-amino]-methyl}-benzamide

The title compound 379 was produced in the same manner as in Example 5.

¹H-NMR (CD₃OD, 400 MHz): δ 8.64 (1H, d, J=9.0 Hz), 8.35 (1H, s), 7.90-8.00 (2H, m), 7.89 (1H, s), 7.70 (1H, d, J=9.8 Hz), 7.56-7.63 (3H, m), 7.53 (1H, dd, J=7.7 Hz), 7.43-7.49 (1H, m), 3.67 (2H, s), 2.69-2.75 (2H, m), 2.54-2.64 (6H, m), 2.28 (3H, s), 1.03 (6H, t, J=7.2 Hz)

Mass spectrometric value (ESI-MS) 536, 538 (M−1)

Compound 380 N-[4-Chloro-2-(4-fluoro-benzylidene-hydrazinocarbonyl)-phenyl]-3-{([(2-diethylamino-ethyl)-methyl-amino]-methyl}-benzamide

The title compound 380 was produced in the same manner as in Example 5.

¹H-NMR (CD₃OD, 400 MHz): δ 8.64 (1H, d, J=9.0 Hz), 8.35 (1H, s), 7.98 (1H, s), 7.94 (1H, d, J=2.2 Hz), 7.87-7.93 (3H, m), 7.58-7.64 (2H, m), 7.53 (1H, dd, J=7.4 Hz, J=7.4 Hz), 7.19 (2H, dd, J=8.8 Hz, J=8.8 Hz), 3.67 (2H, s), 2.68-2.74 (2H, m), 2.53-2.63 (6H, m), 2.28 (3H, s), 1.02 (6H, t, J=7.2 Hz)

Mass spectrometric value (ESI-MS) 536, 538 (M−1)

Compound 381 N-[4-Chloro-2-(3-methyl-benzylidene-hydrazinocarbonyl)-phenyl]-3-{[(2-diethylamino-ethyl)-methyl-amino]-methyl}-benzamide

The title compound 381 was produced in the same manner as in Example 5.

¹H-NMR (CD₃OD, 400 MHz): δ 8.65 (1H, d, J=9.0 Hz), 8.33 (1H, s), 7.99 (1H, s), 7.89-7.96 (2H, m), 7.71 (2H, s), 7.58-7.65 (2H, m), 7.53 (1H, dd, J=7.6 Hz, J=7.6 Hz), 7.25-7.35 (2H, m), 3.67 (2H, s), 2.67-2.75 (2H, m), 2.51-2.62 (6H, m), 2.39 (3H, s), 2.28 (3H, s), 1.01 (6H, t, J=7.2 Hz)

Mass spectrometric value (ESI-MS) 532, 534 (M−1)

Compound 382 N-[4-Chloro-2-(4-methyl-benzylidene-hydrazinocarbonyl)-phenyl]-3-{[(2-diethylamino-ethyl)-methyl-amino]-methyl}-benzamide

The title compound 382 was produced in the same manner as in Example 5.

¹H-NMR (CD₃OD, 400 MHz): δ 8.64 (1H, d, J=9.0 Hz), 8.33 (1H, s), 7.98 (1H, s), 7.88-7.94 (2H, m), 7.73 (2H, d, J=8.3 Hz), 7.58-7.63 (2H, m), 7.52 (1H, dd, J=7.6 Hz, J=7.6 Hz), 7.26 (2H, d, J=8.0 Hz), 3.67 (2H, s), 2.68-2.74 (2H, m), 2.53-2.63 (6H, m), 2.38 (3H, s), 2.28 (3H, s), 1.02 (6H, t, J=7.2 Hz)

Mass spectrometric value (ESI-MS) 532, 534 (M−1)

Compound 383 N-[4-Chloro-2-(3,4-dimethyl-benzylidene-hydrazinocarbonyl)-phenyl]-3-{[(2-diethylamino-ethyl)-methyl-amino]-methyl}-benzamide

The title compound 383 was produced in the same manner as in Example 5.

¹H-NMR (CD₃OD, 400 MHz): δ 8.65 (1H, d, J=9.0 Hz), 8.30 (1H, s), 7.99 (1H, s), 7.89-7.95 (2H, m), 7.66 (1H, s), 7.58-7.64 (2H, m), 7.50-7.57 (2H, m), 7.20 (1H, d, J=8.1 Hz), 3.67 (2H, s), 2.68-2.75 (2H, m), 2.54-2.63 (6H, m), 2.32 (3H, s), 2.31 (3H, s), 2.29 (3H, s), 1.02 (6H, t, J=7.3 Hz)

Mass spectrometric value (ESI-MS) 546, 548 (M−1)

Compound 384 N-[4-Chloro-2-(4-chloro-3-trifluoromethyl-benzylidene-hydrazinocarbonyl)-phenyl]-3-{[(2-diethylamino-ethyl)-methyl-amino]-methyl}-benzamide

The title compound 384 was produced in the same manner as in Example 5.

¹H-NMR (CD₃OD, 400 MHz): δ 8.63 (1H, d, J=8.8 Hz), 8.38 (1H, s), 8.33 (1H, s), 8.03 (1H, d, J=8.3 Hz), 7.95-8.00 (2H, m), 7.92 (1H, d, J=7.8 Hz), 7.68 (1H, d, J=8.3 Hz), 7.57-7.64 (2H, m), 7.53 (1H, s), 3.66 (2H, s), 2.71-2.79 (2H, m), 2.54-2.66 (6H, m), 2.28 (3H, s), 1.03 (6H, t, J=7.2 Hz)

Mass spectrometric value (ESI-MS) 620, 622 (M−1)

Compound 385 N-[4-Chloro-2-(3-methoxy-benzylidene-hydrazinocarbonyl)-phenyl]-3-{[(2-diethylamino-ethyl)-methyl-amino]-methyl}-benzamide

The title compound 385 was produced in the same manner as in Example 5.

¹H-NMR (CD₃OD, 400 MHz): δ 8.64 (1H, d, J=9.0 Hz), 8.33 (1H, s), 7.98 (1H, s), 7.89-7.96 (2H, m), 7.49-7.63 (4H, m), 7.27-7.37 (2H, m), 6.95-7.05 (1H, m), 3.86 (3H, s), 3.66 (2H, s), 2.67-2.73 (2H, m), 2.53-2.62 (6H, m), 2.27 (3H, s), 1.02 (6H, t, J=7.2 Hz)

Mass spectrometric value (ESI-MS) 548, 550 (M−1)

Compound 386 N-[4-Chloro-2-(4-methoxy-benzylidene-hydrazinocarbonyl)-phenyl]-3-{[(2-diethylamino-ethyl)-methyl-amino]-methyl}-benzamide

The title compound 386 was produced in the same manner as in Example 5.

¹H-NMR (CD₃OD, 400 MHz): δ 8.64 (1H, d, J=9.0 Hz), 8.30 (1H, s), 7.98 (1H, s), 7.88-7.95 (2H, m), 7.79 (2H, d, J=9.0 Hz), 7.58-7.64 (2H, m), 7.52 (1H, dd, J=7.7 Hz, J=7.7 Hz), 6.99 (2H, d, J=8.8 Hz), 3.84 (3H, s), 3.66 (2H, s), 2.67-2.73 (2H, m), 2.52-2.62 (6H, m), 2.28 (3H, s), 1.02 (6H, t, J=7.2 Hz)

Mass spectrometric value (ESI-MS) 548, 550 (M−1)

Compound 387 N-[4-Chloro-2-(3-hydroxy-benzylidene-hydrazinocarbonyl)-phenyl]-3-{[(2-diethylamino-ethyl)-methyl-amino]-methyl}-benzamide

The title compound 387 was produced in the same manner as in Example 5.

¹H-NMR (CD₃OD, 400 MHz): δ 8.64 (1H, d, J=9.0 Hz), 8.29 (1H, s), 7.91 (1H, s), 7.88-7.95 (2H, m), 7.61 (2H, dd, J=2.2 Hz, J=9.0 Hz), 7.53 (1H, dd, J=7.7 Hz, J=7.7 Hz), 7.21-7.34 (3H, m), 6.85-6.90 (1H, ddd, J=2.2 Hz, J=2.2 Hz, J=6.8 Hz), 3.67 (2H, s), 2.70-2.75 (2H, m), 2.54-2.64 (6H, m), 2.28 (3H, s), 1.02 (6H, t, J=7.2 Hz)

Mass spectrometric value (ESI-MS) 534, 536 (M−1)

Compound 388 N-[4-Chloro-2-(4-hydroxy-benzylidene-hydrazinocarbonyl)-phenyl]-3-{[(2-diethylamino-ethyl)-methyl-amino]-methyl}-benzamide

The title compound 388 was produced in the same manner as in Example 5.

¹H-NMR (CD₃OD, 400 MHz): δ 8.65 (1H, d, J=9.0 Hz), 8.27 (1H, s), 7.98 (1H, s), 7.88-7.95 (2H, m), 7.70 (2H, d, J=8.8 Hz), 7.61 (2H, dd, J=1.8 Hz, J=8.8 Hz), 7.53 (1H, dd, J=7.7 Hz, J=7.7 Hz), 6.84 (2H, d, J=8.8 Hz), 3.68 (2H, s), 2.76 (2H, t, J=7.3 Hz), 2.55-2.68 (6H, m), 2.29 (3H, s), 1.04 (6H, t, J=7.2 Hz)

Mass spectrometric value (ESI-MS) 534, 536 (M−1)

Compound 389 N-[4-Chloro-2-(3-fluoro-benzylidene-hydrazinocarbonyl)-phenyl]-3-(1H-[1,2,4]triazol-3-ylsulfanylmethyl)-benzamide

The title compound 389 was produced in the same manner as in Example 4.

Mass spectrometric value (ESI-MS) 506 (M−1)

Compound 390 N-[4-Chloro-2-(4-fluoro-benzylidene-hydrazinocarbonyl)-phenyl]-3-(1H-[1,2,4]triazol-3-ylsulfanylmethyl)-benzamide

The title compound 390 was produced in the same manner as in Example 4.

Mass spectrometric value (ESI-MS) 506 (M−1)

Compound 391 N-[4-Chloro-2-(3-methyl-benzylidene-hydrazinocarbonyl)-phenyl]-3-(1H-[1,2,4]triazol-3-ylsulfanylmethyl)-benzamide

The title compound 391 was produced in the same manner as in Example 4.

Mass spectrometric value (ESI-MS) 503, 504 (M−1)

Compound 392 N-[4-Chloro-2-(4-methyl-benzylidene-hydrazinocarbonyl)-phenyl]-3-(1H-[1,2,4]triazol-3-ylsulfanylmethyl)-benzamide

The title compound 392 was produced in the same manner as in Example 4.

Mass spectrometric value (ESI-MS) 503, 504 (M−1)

Compound 393 N-[4-Chloro-2-(4-chloro-3-trifluoromethyl-benzylidene-hydrazinocarbonyl)-phenyl]-3-(1H-[1,2,4]triazol-3-ylsulfanylmethyl)-benzamide

The title compound 393 was produced in the same manner as in Example 4.

Mass spectrometric value (ESI-MS) 591, 593 (M−1)

Compound 394 N-[4-Chloro-2-(3-fluoro-benzylidene-hydrazinocarbonyl)-phenyl]-3-{[(2-hydroxy-ethyl)-methyl-amino]-methyl}-benzamide

The title compound 394 was produced in the same manner as in Example 5.

¹H-NMR (CD₃OD, 400 MHz): δ 8.64 (1H, d, J=9.0 Hz), 8.35 (1H, s), 8.00 (1H, s), 7.88-7.95 (2H, m), 7.71 (1H, d, J=9.3 Hz), 7.58-7.67 (3H, m), 7.53 (1H, dd, J=7.7 Hz, J=7.7 Hz), 7.42-7.50 (1H, m), 7.15-7.22 (1H, m), 3.69-3.74 (4H, m), 2.62 (2H, t, J=6.0 Hz), 2.30 (3H, s)

Mass spectrometric value (ESI-MS) 481, 483 (M−1)

Compound 395 N-[4-Chloro-2-(4-fluoro-benzylidene-hydrazinocarbonyl)-phenyl]-3-{[(2-hydroxy-ethyl)-methyl-amino]-methyl}-benzamide

The title compound 395 was produced in the same manner as in Example 5.

¹H-NMR (CD₃OD, 400 MHz): δ 8.63 (1H, d, J=9.0 Hz), 8.35 (1H, s), 7.95-8.02 (2H, m), 7.87-7.95 (3H, m), 7.63 (1H, d, J=9.0 Hz), 7.62 (1H, d, J=9.0 Hz), 7.52 (1H, dd, J=7.7 Hz, J=7.7 Hz), 7.19 (2H, dd, J=8.8 Hz, J=8.8 Hz), 3.69-3.75 (4H, m), 2.62 (2H, t, J=6.0 Hz), 2.30 (3H, s)

Mass spectrometric value (ESI-MS) 481, 483 (M−1)

Compound 396 N-[4-Chloro-2-(3-methyl-benzylidene-hydrazinocarbonyl)-phenyl]-3-{[(2-hydroxy-ethyl)-methyl-amino]-methyl}-benzamide

The title compound 396 was produced in the same manner as in Example 5.

¹H-NMR (CD₃OD, 400 MHz): δ 8.65 (1H, d, J=8.8 Hz), 8.33 (1H, s), 7.99 (1H, s), 7.88-7.95 (3H, m), 7.71 (1H, s), 7.60-7.65 (3H, m), 7.52 (1H, dd, J=7.6 Hz, J=7.6 Hz), 7.25-7.36 (2H, m), 3.68-3.74 (4H, m), 2.61 (2H, t, J=6.0 Hz), 2.39 (3H, s), 2.29 (3H, s)

Mass spectrometric value (ESI-MS) 477 (M−1)

Compound 397 N-[4-Chloro-2-(4-methyl-benzylidene-hydrazinocarbonyl)-phenyl]-3-{[(2-hydroxy-ethyl)-methyl-amino]-methyl}-benzamide

The title compound 397 was produced in the same manner as in Example 5.

¹H-NMR (CD₃OD, 400 MHz): δ 8.64 (1H, d, J=9.0 Hz), 8.33 (1H, s), 8.00 (1H, bs), 7.90-7.95 (2H, m), 7.74 (2H, d, J=7.8 Hz), 7.60-7.65 (2H, m), 7.53 (1H, dd, J=7.7 Hz, J=7.7 Hz), 7.27 (2H, d, J=7.8 Hz), 3.70-3.78 (4H, m), 2.65 (2H, t, J=6.0 Hz), 2.38 (3H, s), 2.32 (3H, s)

Mass spectrometric value (ESI-MS) 477 (M−1)

Compound 398 N-[4-Chloro-2-(3,4-dimethyl-benzylidene-hydrazinocarbonyl)-phenyl]-3-{[(2-hydroxy-ethyl)-methyl-amino]-methyl}-benzamide

The title compound 398 was produced in the same manner as in Example 5.

¹H-NMR (CD₃OD, 400 MHz): δ 8.65 (1H, d, J=9.0 Hz), 8.30 (1H, s), 8.00 (1H, bs), 7.90-7.95 (2H, m), 7.66 (1H, s), 7.59-7.65 (2H, m), 7.50-7.57 (2H, m), 7.20 (1H, d, J=7.8 Hz), 3.76 (2H, s), 3.73 (2H, t, J=6.0 Hz), 2.66 (2H, t, J=6.0 Hz), 2.33 (3H, s), 2.31 (3H, s), 2.30 (3H, s)

Mass spectrometric value (ESI-MS) 491 (M−1)

Compound 399 N-[4-Chloro-2-(4-chloro-3-trifluoromethyl-benzylidene-hydrazinocarbonyl)-phenyl]-3-{[(2-hydroxy-ethyl)-methyl-amino]-methyl}-benzamide

The title compound 399 was produced in the same manner as in Example 5.

¹H-NMR (CD₃OD, 400 MHz): δ 8.63 (1H, d, J=9.0 Hz), 8.39 (1H, s), 8.34 (1H, s), 8.03-8.08 (1H, m), 8.00 (1H, s), 7.94 (1H, d, J=2.4 Hz), 7.90 (1H, d, J=8.3 Hz), 7.70 (1H, d, J=8.5 Hz), 7.58-7.67 (2H, m), 7.52 (1H, dd, J=7.6 Hz, J=7.6 Hz), 3.68-3.74 (4H, m), 2.60 (2H, t, J=6.0 Hz), 2.28 (3H, s)

Mass spectrometric value (ESI-MS) 565 (M−1)

Compound 400 N-[4-Chloro-2-(3-methoxy-benzylidene-hydrazinocarbonyl)-phenyl]-3-{[(2-hydroxy-ethyl)-methyl-amino]-methyl}-benzamide

The title compound 400 was produced in the same manner as in Example 5.

¹H-NMR (CD₃OD, 400 MHz): δ 8.64 (1H, d, J=9.0 Hz), 8.33 (1H, s), 7.99 (1H, s), 7.88-7.94 (2H, m), 7.58-7.64 (2H, m), 7.57 (1H, s), 7.48-7.54 (1H, m), 7.26-7.36 (2H, m), 6.97-7.02 (1H, m), 3.86 (3H, s), 3.68-3.74 (4H, m), 2.61 (2H, t, J=6.1 Hz), 2.29 (3H, s)

Mass spectrometric value (ESI-MS) 493, 495 (M−1)

Compound 401 N-[4-Chloro-2-(4-methoxy-benzylidene-hydrazinocarbonyl)-phenyl]-3-{[(2-hydroxy-ethyl)-methyl-amino]-methyl}-benzamide

The title compound 401 was produced in the same manner as in Example 5.

¹H-NMR (CD₃OD, 400 MHz): δ 8.65 (1H, d, J=9.0 Hz), 8.31 (1H, s), 7.99 (1H, s), 7.75-7.93 (5H, m), 7.58-7.65 (2H, m), 7.53 (1H, dd, J=7.7 Hz, J=7.7 Hz), 7.00 (1H, d, J=8.8 Hz), 3.85 (3H, s), 3.67-3.74 (4H, m), 2.63 (2H, t, J=6.1 Hz), 2.31 (3H, s)

Mass spectrometric value (ESI-MS) 493, 494 (M−1)

Compound 402 N-[4-Chloro-2-(3-hydroxy-benzylidene-hydrazinocarbonyl)-phenyl]-3-{[(2-hydroxy-ethyl)-methyl-amino]-methyl}-benzamide

The title compound 402 was produced in the same manner as in Example 5.

¹H-NMR (CD₃OD, 400 MHz): δ 8.63 (1H, d, J=9.0 Hz), 8.29 (1H, s), 7.99 (1H, s), 7.88-7.94 (3H, m), 7.62 (2H, d, J=7.8 Hz), 7.52 (1H, dd, J=7.7 Hz, J=7.7 Hz), 7.31 (1H, bs), 7.23-7.28 (2H, m), 3.68-3.74 (4H, m), 2.61 (2H, t, J=6.1 Hz), 2.29 (3H, s)

Mass spectrometric value (ESI-MS) 479 (M−1)

Compound 403 N-[4-Chloro-2-(4-hydroxy-benzylidene-hydrazinocarbonyl)-phenyl]-3-{[(2-hydroxy-ethyl)-methyl-amino]-methyl}-benzamide

The title compound 403 was produced in the same manner as in Example 5.

¹H-NMR (CD₃OD, 400 MHz): δ 8.65 (1H, d, J=9.0 Hz), 8.27 (1H, s), 7.99 (1H, s), 7.89-7.94 (3H, m), 7.71 (2H, d, J=8.7 Hz), 7.58-7.65 (2H, m), 7.52 (1H, dd, J=7.7 Hz, J=7.7 Hz), 6.84 (2H, d, J=8.7 Hz), 3.71 (2H, t, J=6.1 Hz), 3.70 (2H, s), 2.61 (2H, t, J=6.1 Hz), 2.29 (3H, s)

Mass spectrometric value (ESI-MS) 479, 481 (M−1)

Compound 404 3-{[Bis-(2-hydroxy-ethyl)-amino]-methyl}-N-[4-chloro-2-(3-methyl-benzylidene-hydrazinocarbonyl)-phenyl]-benzamide

The title compound 404 was produced in the same manner as in Example 5.

¹H-NMR (CD₃OD, 400 MHz): δ 8.67 (1H, d, J=9.0 Hz), 8.34 (1H, s), 8.07 (1H, s), 7.94 (1H, d, J=2.4 Hz), 7.90 (1H, d, J=7.8 Hz), 7.74 (1H, s), 7.61-7.66 (3H, m), 7.51 (1H, dd, J=7.7 Hz, J=7.7 Hz), 7.25-7.37 (2H, m), 3.83 (2H, s), 3.66 (4H, t, J=5.9 Hz), 2.71 (4H, t, J=5.9 Hz), 2.40 (3H, s)

Mass spectrometric value (ESI-MS) 507, 509 (M−1)

Compound 405 3-{[Bis-(2-hydroxy-ethyl)-amino]-methyl}-N-[4-chloro-2-(4-methyl-benzylidene-hydrazinocarbonyl)-phenyl]-benzamide

The title compound 405 was produced in the same manner as in Example 5.

Mass spectrometric value (ESI-MS) 507, 508 (M−1)

Compound 406 3-{[Bis-(2-hydroxy-ethyl)-amino]-methyl}-N-[4-chloro-2-(3,4-dimethyl-benzylidene-hydrazinocarbonyl)-phenyl]-benzamide

The title compound 406 was produced in the same manner as in Example 5.

¹H-NMR (CD₃OD, 400 MHz): δ 8.67 (1H, d, J=9.0 Hz), 8.30 (1H, s), 8.06 (1H, s), 7.92 (1H, d, J=2.4 Hz), 7.87-7.91 (1H, m), 7.68 (1H, s), 7.60-7.65 (2H, m), 7.47-7.58 (2H, m), 7.20 (1H, d, J=7.8 Hz), 3.83 (2H, s), 3.65 (4H, t, J=5.8 Hz), 2.71 (4H, t, J=5.8 Hz), 2.32 (3H, s), 2.30 (3H, s)

Mass spectrometric value (ESI-MS) 521, 522 (M−1)

Compound 407 3-{[Bis-(2-hydroxy-ethyl)-amino]-methyl}-N-[4-chloro-2-(4-chloro-3-trifluoromethyl-benzylidene-hydrazinocarbonyl)-phenyl]-benzamide

The title compound 407 was produced in the same manner as in Example 5.

¹H-NMR (CD₃OD, 400 MHz): δ 8.66 (1H, d, J=8.8 Hz), 8.39 (1H, s), 8.37 (1H, s), 8.05-8.10 (2H, m), 7.95 (1H, d, J=2.2 Hz), 7.84-7.92 (1H, m), 7.70 (1H, d, J=8.3 Hz), 7.60-7.68 (2H, m), 7.48-7.53 (1H, dd, J=7.8 Hz, J=7.8 Hz), 3.83 (2H, s), 3.65 (4H, t, J=5.8 Hz), 2.71 (4H, t, J=5.8 Hz)

Mass spectrometric value (ESI-MS) 595, 597 (M−1)

Compound 408 3-{[Bis-(2-hydroxy-ethyl)-amino]-methyl}-N-[4-chloro-2-(3-methoxy-benzylidene-hydrazinocarbonyl)-phenyl]-benzamide

The title compound 408 was produced in the same manner as in Example 5.

¹H-NMR (CD₃OD, 400 MHz): δ 8.66 (1H, d, J=9.0 Hz), 8.33 (1H, s), 8.06 (1H, s), 7.89-7.96 (2H, m), 7.58-7.66 (3H, m), 7.48-7.54 (1H, m), 7.28-7.38 (2H, m), 6.97-7.04 (1H, m), 3.87 (3H, s), 3.85 (2H, s), 3.66 (4H, t, J=5.9 Hz), 2.72 (4H, t, J=5.9 Hz)

Mass spectrometric value (ESI-MS) 523, 525 (M−1)

Compound 409 3-{[Bis-(2-hydroxy-ethyl)-amino]-methyl}-N-[4-chloro-2-(4-methoxy-benzylidene-hydrazinocarbonyl)-phenyl]-benzamide

The title compound 409 was produced in the same manner as in Example 5.

¹H-NMR (CD₃OD, 400 MHz): δ 8.66 (1H, d, J=9.0 Hz), 8.31 (1H, s), 8.06 (1H, s), 7.80-7.94 (4H, m), 7.60-7.66 (2H, m), 7.50 (1H, dd, J=7.7 Hz, J=7.7 Hz), 7.00 (1H, d, J=9.0 Hz), 3.90 (3H, s), 3.85 (2H, s), 3.66 (4H, t, J=5.9 Hz), 2.71 (4H, t, J=5.9 Hz)

Mass spectrometric value (ESI-MS) 523, 525 (M−1)

Compound 410 3-{[Bis-(2-hydroxy-ethyl)-amino]-methyl}-N-[4-chloro-2-(3-hydroxy-benzylidene-hydrazinocarbonyl)-phenyl]-benzamide

The title compound 410 was produced in the same manner as in Example 5.

¹H-NMR (CD₃OD, 400 MHz): δ 8.65 (1H, d, J=9.0 Hz), 8.29 (1H, s), 8.05 (1H, s), 7.93 (1H, d, J=2.4 Hz), 7.87-7.92 (1H, m), 7.60-7.66 (2H, m), 7.50 (1H, dd, J=7.7 Hz, J=7.7 Hz), 7.33 (1H, s), 7.26 (2H, d, J=4.9 Hz), 6.85-6.92 (1H, m), 3.83 (2H, s), 3.66 (4H, t, J=5.9 Hz), 2.71 (4H, t, J=5.9 Hz)

Mass spectrometric value (ESI-MS) 509 (M−1)

Compound 411 3-{[Bis-(2-hydroxy-ethyl)-amino]-methyl}-N-[4-chloro-2-(4-hydroxy-benzylidene-hydrazinocarbonyl)-phenyl]-benzamide

The title compound 411 was produced in the same manner as in Example 5.

¹H-NMR (CD₃OD, 400 MHz): δ 8.67 (1H, d, J=9.0 Hz), 8.27 (1H, s), 8.06 (1H, s), 7.85-7.93 (2H, m), 7.72 (2H, d, J=8.8 Hz), 7.60-7.65 (2H, m), 7.47-7.54 (1H, m), 6.85 (2H, d, J=8.6 Hz), 3.83 (2H, s), 3.65 (4H, t, J=5.9 Hz), 2.71 (4H, t, J=5.9 Hz)

Mass spectrometric value (ESI-MS) 509, 511 (M−1)

Compound 412 N-[4-Chloro-2-(3-fluoro-benzylidene-hydrazinocarbonyl)-phenyl]-4-{[(2-hydroxy-ethyl)-methyl-amino]-methyl}-benzamide

The title compound 412 was produced in the same manner as in Example 5.

¹H-NMR (CD₃OD, 400 MHz): δ 8.65 (1H, d, J=9.0 Hz), 8.36 (1H, s), 7.98 (2H, d, J=8.3 Hz), 7.94 (1H, d, J=2.4 Hz), 7.68-7.74 (1H, m), 7.58-7.65 (2H, m), 7.55 (2H, d, J=8.3 Hz), 7.43-7.50 (1H, m), 7.10-7.23 (1H, m), 3.69 (2H, t, J=6.1 Hz), 3.67 (2H, s), 2.58 (2H, t, J=6.1 Hz), 2.28 (3H, s)

Mass spectrometric value (ESI-MS) 482 (M−1)

Compound 413 N-[4-Chloro-2-(4-fluoro-benzylidene-hydrazinocarbonyl)-phenyl]-4-{[(2-hydroxy-ethyl)-methyl-amino]-methyl}-benzamide

The title compound 413 was produced in the same manner as in Example 5.

¹H-NMR (CD₃OD, 400 MHz): δ 8.65 (1H, d, J=9.0 Hz), 8.36 (1H, s), 7.98 (2H, d, J=8.3 Hz), 7.87-7.95 (3H, m), 7.63 (1H, dd, J=2.4 Hz, J=9.0 Hz), 7.55 (2H, d, J=7.8 Hz), 7.19 (2H, dd, J=8.7 Hz, J=8.7 Hz), 3.69 (2H, t, J=6.0 Hz), 3.67 (2H, s), 2.58 (2H, t, J=6.0 Hz), 2.28 (3H, s)

Mass spectrometric value (ESI-MS) 481, 483 (M−1)

Compound 414 N-[4-Chloro-2-(3-methyl-benzylidene-hydrazinocarbonyl)-phenyl]-4-{[(2-hydroxy-ethyl)-methyl-amino]-methyl}-benzamide

The title compound 414 was produced in the same manner as in Example 5.

¹H-NMR (CD₃OD, 400 MHz): δ 8.66 (1H, d, J=9.0 Hz), 8.34 (1H, s), 7.98 (2H, d, J=8.0 Hz), 7.93 (1H, d, J=2.4 Hz), 7.72 (1H, s), 7.60-7.65 (2H, m), 7.55 (2H, d, J=8.0 Hz), 7.26-7.36 (2H, m), 3.69 (2H, t, J=6.1 Hz), 3.67 (2H, s), 2.58 (2H, t, J=6.1 Hz), 2.40 (3H, s), 2.28 (3H, s)

Mass spectrometric value (ESI-MS) 477, 479 (M−1)

Compound 415 N-[4-Chloro-2-(4-methyl-benzylidene-hydrazinocarbonyl)-phenyl]-4-{[(2-hydroxy-ethyl)-methyl-amino]-methyl}-benzamide

The title compound 415 was produced in the same manner as in Example 5.

¹H-NMR (CD₃OD, 400 MHz): δ 8.66 (1H, d, J=9.0 Hz), 8.33 (1H, s), 7.98 (2H, d, J=8.0 Hz), 7.93 (1H, d, J=2.5 Hz), 7.74 (2H, d, J=8.0 Hz), 7.62 (1H, dd, J=2.5 Hz, J=9.0 Hz), 7.55 (2H, d, J=8.0 Hz), 7.27 (2H, d, J=7.8 Hz), 3.69 (2H, t, J=6.1 Hz), 3.67 (3H, s), 2.58 (2H, t, J=6.1 Hz), 2.39 (3H, s), 2.27 (3H, s)

Mass spectrometric value (ESI-MS) 477 (M−1)

Compound 416 N-[4-Chloro-2-(3,4-dimethyl-benzylidene-hydrazinocarbonyl)-phenyl]-4-{[(2-hydroxy-ethyl)-methyl-amino]-methyl}-benzamide

The title compound 416 was produced in the same manner as in Example 5.

¹H-NMR (CD₃OD, 400 MHz): δ 8.66 (1H, d, J=9.0 Hz), 8.30 (1H, s), 7.98 (2H, d, J=8.3 Hz), 7.92 (1H, d, J=2.4 Hz), 7.66 (1H, s), 7.61 (1H, dd, J=2.4 Hz, J=9.0 Hz), 7.52-7.57 (3H, m), 7.20 (1H, d, J=8.0 Hz), 3.69 (2H, d, J=8.0 Hz), 3.67 (2H, s), 2.58 (2H, t, J=6.1 Hz), 2.32 (3H, s), 2.30 (3H, s), 2.27 (3H, s)

Mass spectrometric value (ESI-MS) 491, 493 (M−1)

Compound 417 N-[4-Chloro-2-(4-chloro-3-trifluoromethyl-benzylidene-hydrazinocarbonyl)-phenyl]-4-{[(2-hydroxy-ethyl)-methyl-amino]-methyl}-benzamide

The title compound 417 was produced in the same manner as in Example 5.

¹H-NMR (CD₃OD, 400 MHz): δ 8.55 (1H, d, J=9.0 Hz), 8.30 (1H, s), 8.25 (1H, s), 7.93-7.98 (1H, m), 7.83-7.90 (3H, m), 7.60 (1H, d, J=8.3 Hz), 7.54 (1H, dd, J=2.3 Hz, J=8.8 Hz), 7.46 (2H, d, J=8.3 Hz), 3.59 (2H, t, J=6.0 Hz), 3.58 (2H, s), 2.49 (2H, t, J=6.0 Hz), 2.18 (3H, s)

Mass spectrometric value (ESI-MS) 565, 567 (M−1)

Compound 418 N-[4-Chloro-2-(3-methoxy-benzylidene-hydrazinocarbonyl)-phenyl]-4-{[(2-hydroxy-ethyl)-methyl-amino]-methyl}-benzamide

The title compound 418 was produced in the same manner as in Example 5.

¹H-NMR (CD₃OD, 400 MHz): δ 8.56 (1H, d, J=9.0 Hz), 8.24 (1H, s), 7.82-7.90 (3H, m), 7.42-7.55 (4H, m), 7.18-7.27 (2H, m), 6.88-6.94 (1H, m), 3.77 (3H, s), 3.56-3.61 (4H, m), 2.50 (2H, t, J=6.0 Hz), 2.18 (3H, s)

Mass spectrometric value (ESI-MS) 493, 495 (M−1)

Compound 419 N-[4-Chloro-2-(4-methoxy-benzylidene-hydrazinocarbonyl)-phenyl]-4-{[(2-hydroxy-ethyl)-methyl-amino]-methyl}-benzamide

The title compound 419 was produced in the same manner as in Example 5.

¹H-NMR (CD₃OD, 400 MHz): δ 8.56 (1H, d, J=9.0 Hz), 8.21 (1H, s), 7.88 (2H, d, J=8.3 Hz), 7.81 (1H, d, J=2.2 Hz), 7.69 (2H, d, J=8.8 Hz), 7.50 (1H, dd, J=2.4 Hz, J=8.8 Hz), 7.45 (2H, d, J=8.3 Hz), 6.89 (2H, d, J=8.8 Hz), 3.75 (3H, s), 3.59 (2H, t, J=6.1 Hz), 3.59 (2H, s), 2.50 (2H, t, J=6.1 Hz), 2.19 (3H, s)

Mass spectrometric value (ESI-MS) 493, 495 (M−1)

Compound 420 N-[4-Chloro-2-(3-hydroxy-benzylidene-hydrazinocarbonyl)-phenyl]-4-{[(2-hydroxy-ethyl)-methyl-amino]-methyl}-benzamide

The title compound 420 was produced in the same manner as in Example 5.

¹H-NMR (CD₃OD, 400 MHz): δ 8.55 (1H, d, J=8.8 Hz), 8.19 (1H, s), 7.88 (2H, d, J=7.8 Hz), 7.82-7.85 (1H, m), 7.50-7.55 (1H, m), 7.46 (2H, d, J=7.6 Hz), 7.22 (1H, s), 7.13-7.18 (2H, m), 6.75-6.82 (1H, m), 3.56-3.62 (4H, m), 2.49 (2H, t, J=6.1 Hz), 2.19 (3H, s)

Mass spectrometric value (ESI-MS) 479, 481 (M−1)

Compound 421 N-[4-Chloro-2-(4-hydroxy-benzylidene-hydrazinocarbonyl)-phenyl]-4-{[(2-hydroxy-ethyl)-methyl-amino]-methyl}-benzamide

The title compound 421 was produced in the same manner as in Example 5.

Mass spectrometric value (ESI-MS) 479, 481 (M−1)

Compound 422 N-[4-Chloro-2-(3-fluoro-benzylidene-hydrazinocarbonyl)-phenyl]-3-{[ethyl-(2-hydroxy-ethyl)-amino]-methyl}-benzamide

The title compound 422 was produced in the same manner as in Example 5.

¹H-NMR (CD₃OD, 400 MHz): δ 8.55 (1H, d, J=9.0 Hz), 8.26 (1H, s), 7.93 (1H, s), 7.84 (1H, d, J=2.4 Hz), 7.78-7.83 (1H, m), 7.33-7.70 (6H, m), 7.05-7.20 (1H, m), 3.72 (2H, s), 3.57 (2H, t, J=6.1 Hz), 2.59 (2H, t, J=6.0 Hz), 2.54 (3H, q, J=7.3 Hz), 1.02 (3H, t, J=7.1 Hz)

Mass spectrometric value (ESI-MS) 495 (M−1)

Compound 423 N-[4-Chloro-2-(4-fluoro-benzylidene-hydrazinocarbonyl)-phenyl]-3-{[ethyl-(2-hydroxy-ethyl)-amino]-methyl}-benzamide

The title compound 423 was produced in the same manner as in Example 5.

¹H-NMR (CD₃OD, 400 MHz): δ 8.54 (1H, d, J=9.0 Hz), 8.26 (1H, s), 7.92 (1H, s), 7.77-7.85 (4H, m), 7.53 (2H, dd, J=2.2 Hz, J=9.0 Hz), 7.41 (1H, dd, J=7.7. Hz, J=7.7. Hz), 7.09 (2H, dd, J=8.8 Hz, J=8.8 Hz), 3.68 (2H, s), 3.57 (2H, t, J=6.2 Hz), 2.57 (2H, t, J=6.3 Hz), 2.53 (2H, q, J=7.1 Hz), 1.01 (3H, t, J=7.2 Hz)

Mass spectrometric value (ESI-MS) 495 (M−1)

Compound 424 N-[4-Chloro-2-(3-methyl-benzylidene-hydrazinocarbonyl)-phenyl]-3-{[ethyl-(2-hydroxy-ethyl)-amino]-methyl}-benzamide

The title compound 424 was produced in the same manner as in Example 5.

¹H-NMR (CD₃OD, 400 MHz): δ 8.56 (1H, d, J=9.0 Hz), 8.24 (1H, s), 7.92 (1H, s), 7.83 (1H, d, J=2.4 Hz), 7.78-7.82 (1H, m), 7.62 (1H, s), 7.53 (2H, dd, J=2.2 Hz, J=9.0 Hz), 7.42 (2H, dd, J=7.4 Hz, J=7.4 Hz), 7.15-7.26 (2H, m), 3.69 (2H, s), 3.57 (2H, t, J=6.3 Hz), 2.57 (2H, t, J=6.3 Hz), 2.53 (2H, q, J=7.2 Hz), 2.30 (3H, s), 1.01 (3H, t, J=7.2 Hz)

Mass spectrometric value (ESI-MS) 491 (M−1), 515 (M+23)

Compound 425 N-[4-Chloro-2-(4-methyl-benzylidene-hydrazinocarbonyl)-phenyl]-3-{[ethyl-(2-hydroxy-ethyl)-amino]-methyl}-benzamide

The title compound 425 was produced in the same manner as in Example 5.

¹H-NMR (CD₃OD, 400 MHz): δ 8.65 (1H, d, J=9.0 Hz), 8.33 (1H, s), 8.01 (1H, s), 7.88-7.94 (2H, m), 7.74 (2H, d, J=8.1 Hz), 7.60-7.65 (2H, m), 7.51 (2H, m), 7.26 (2H, d, J=8.1 Hz), 3.80 (2H, s), 3.67 (2H, t, J=6.2 Hz), 2.69 (2H, t, J=6.2 Hz), 2.64 (2H, q, J=7.1 Hz), 2.38 (3H, s), 1.11 (3H, t, J=7.2 Hz)

Mass spectrometric value (ESI-MS) 491 (M−1), 515 (M+23)

Compound 426 N-[4-Chloro-2-(3,4-dimethyl-benzylidene-hydrazinocarbonyl)-phenyl]-3-{[ethyl-(2-hydroxy-ethyl)-amino]-methyl}-benzamide

The title compound 426 was produced in the same manner as in Example 5.

¹H-NMR (CD₃OD, 400 MHz): δ 8.66 (1H, d, J=9.0 Hz), 8.30 (1H, s), 8.02 (1H, s), 7.89-7.94 (2H, m), 7.60-7.69 (3H, m), 7.49-7.57 (2H, m), 7.21 (1H, d, J=7.8 Hz), 3.82 (2H, s), 3.68 (2H, t, J=6.2 Hz), 2.70 (2H, t, J=6.2 Hz), 2.66 (2H, q, J=7.1 Hz), 2.32 (3H, s), 2.30 (3H, s), 1.12 (3H, t, J=7.2 Hz)

Mass spectrometric value (ESI-MS) 505 (M−1)

Compound 427 N-[4-Chloro-2-(4-chloro-3-trifluoromethyl-benzylidene-hydrazinocarbonyl)-phenyl]-3-{[ethyl-(2-hydroxy-ethyl)-amino]-methyl}-benzamide

The title compound 427 was produced in the same manner as in Example 5.

Mass spectrometric value (ESI-MS) 579 (M−1)

Compound 428 N-[4-Chloro-2-(3-methoxy-benzylidene-hydrazinocarbonyl)-phenyl]-3-{[ethyl-(2-hydroxy-ethyl)-amino]-methyl}-benzamide

The title compound 428 was produced in the same manner as in Example 5.

¹H-NMR (CD₃OD, 400 MHz): δ 8.65 (1H, d, J=8.8 Hz), 8.33 (1H, s), 8.01 (1H, s), 7.93 (1H, d, J=2.2. Hz), 7.89 (1H, d, J=2.2. Hz), 7.56-7.66 (3H, m), 7.50 (1H, dd, J=7.7 Hz, J=7.7 Hz), 7.29-7.37 (2H, m), 6.97-7.04 (1H, m), 3.86 (3H, s), 3.77 (2H, s), 3.66 (2H, t, J=6.2 Hz), 2.66 (2H, t, J=6.4 Hz), 2.61 (2H, q, J=7.4 Hz), 1.10 (3H, t, J=7.2 Hz)

Mass spectrometric value (ESI-MS) 507 (M−1)

Compound 429 N-[4-Chloro-2-(4-methoxy-benzylidene-hydrazinocarbonyl)-phenyl]-3-{[ethyl-(2-hydroxy-ethyl)-amino]-methyl}-benzamide

The title compound 429 was produced in the same manner as in Example 5.

¹H-NMR (CD₃OD, 400 MHz): δ 8.65 (1H, d, J=9.0 Hz), 8.30 (1H, s), 8.01 (1H, s), 7.91 (1H, d, J=2.4 Hz), 7.87-7.91 (1H, m), 7.80 (2H, d, J=8.8 Hz), 7.59-7.65 (2H, m), 7.51 (1H, dd, J=7.7 Hz, J=7.7 Hz), 6.99 (2H, d, J=8.8 Hz), 3.85 (3H, s), 3.78 (2H, s), 3.66 (2H, t, J=6.2 Hz), 2.67 (2H, t, J=6.3 Hz), 2.62 (2H, q, J=7.2 Hz), 1.10 (3H, t, J=7.1 Hz)

Mass spectrometric value (ESI-MS) 507 (M−1)

Compound 430 N-[4-Chloro-2-(3-hydroxy-benzylidene-hydrazinocarbonyl)-phenyl]-3-{[ethyl-(2-hydroxy-ethyl)-amino]-methyl}-benzamide

The title compound 430 was produced in the same manner as in Example 5.

¹H-NMR (CD₃OD, 400 MHz): δ 8.65 (1H, d, J=8.8 Hz), 8.29 (1H, s), 8.01 (1H, s), 7.93 (1H, d, J=2.2 Hz), 7.89 (1H, d, J=7.6 Hz), 7.60-7.66 (2H, m), 7.51 (1H, dd, J=7.6 Hz, J=7.6 Hz), 7.22-7.40 (3H, m), 3.78 (2H, s), 3.66 (2H, t, J=6.4 Hz), 2.67 (2H, t, J=6.4 Hz), 2.62 (2H, q, J=7.3 Hz), 1.10 (3H, t, J=7.2 Hz)

Mass spectrometric value (ESI-MS) 493 (M−1)

Compound 431 N14-Chloro-2-(4-hydroxy-benzylidene-hydrazinocarbonyl)-phenyl]-3-{[ethyl-(2-hydroxy-ethyl)-amino]-methyl}-benzamide

The title compound 431 was produced in the same manner as in Example 5.

¹H-NMR (CD₃OD, 400 MHz): δ 8.65 (1H, d, J=8.8 Hz), 8.27 (1H, s), 8.00 (1H, s), 7.86-7.94 (2H, m), 7.70 (2H, d, J=8.8 Hz), 7.58-7.65 (2H, m), 7.50 (1H, dd, J=7.7 Hz, J=7.7 Hz), 6.84 (2H, d, J=8.6 Hz), 3.77 (2H, s), 3.66 (2H, t, J=6.3 Hz), 2.66 (2H, t, J=6.3 Hz), 2.62 (2H, q, J=7.2 Hz), 1.10 (3H, t, J=7.1 Hz)

Mass spectrometric value (ESI-MS) 493 (M−1)

Compound 432 N-[4-Chloro-2-(3-fluoro-benzylidene-hydrazinocarbonyl)-phenyl]-4-{[ethyl-(2-hydroxy-ethyl)-amino]-methyl}-benzamide

The title compound 432 was produced in the same manner as in Example 5.

¹H-NMR (CD₃OD, 400 MHz): δ 8.65 (1H, d, J=9.0 Hz), 8.36 (1H, s), 7.92-8.00 (3H, m), 7.71 (1H, d, J=9.5 Hz), 7.54-7.65 (4H, m), 7.43-7.51 (1H, m), 7.15-7.23 (1H, m), 3.75 (2H, s), 3.63 (2H, t, J=6.2 Hz), 2.64 (2H, t, J=6.2 Hz), 2.60 (2H, q, J=7.3 Hz), 1.09 (3H, t, J=7.1 Hz)

Mass spectrometric value (ESI-MS) 495 (M−1)

Compound 433 N-[4-Chloro-2-(4-fluoro-benzylidene-hydrazinocarbonyl)-phenyl]-4-{[ethyl-(2-hydroxy-ethyl)-amino]-methyl}-benzamide

The title compound 433 was produced in the same manner as in Example 5.

¹H-NMR (CD₃OD, 400 MHz): δ 8.65 (1H, d, J=8.8 Hz), 8.35 (1H, s), 7.96 (2H, d, J=8.3 Hz), 7.87-7.94 (3H, m), 7.61 (1H, dd, J=2.4 Hz, J=9.0 Hz), 7.55 (2H, d, J=8.0 Hz), 7.19 (2H, dd, J=8.8 Hz, J=8.8 Hz), 3.74 (2H, s), 3.63 (2H, t, J=6.2 Hz), 2.64 (2H, t, J=6.3 Hz), 2.60 (2H, q, J=7.2 Hz), 1.09 (3H, t, J=7.1 Hz)

Mass spectrometric value (ESI-MS) 495 (M−1)

Compound 434 N-[4-Chloro-2-(3-methyl-benzylidene-hydrazinocarbonyl)-phenyl]-4-{[ethyl-(2-hydroxy-ethyl)-amino]-methyl}-benzamide

The title compound 434 was produced in the same manner as in Example 5.

¹H-NMR (CD₃OD, 400 MHz): δ 8.66 (1H, d, J=8.8 Hz), 8.33 (1H, s), 7.97 (2H, d, J=8.3 Hz), 7.93 (1H, d, J=2.4 Hz), 7.12 (1H, s), 7.60-7.65 (2H, m), 7.56 (2H, d, J=8.3 Hz), 7.25-7.36 (2H, m), 3.74 (2H, s), 3.63 (2H, t, J=6.2 Hz), 2.64 (2H, t, J=6.3 Hz), 2.60 (2H, q, J=7.1 Hz), 2.40 (3H, s), 1.09 (3H, t, J=7.1 Hz)

Mass spectrometric value (ESI-MS) 491 (M−1)

Compound 435 N-[4-Chloro-2-(4-methyl-benzylidene-hydrazinocarbonyl)-phenyl]-4-{[ethyl-(2-hydroxy-ethyl)-amino]-methyl}-benzamide

The title compound 435 was produced in the same manner as in Example 5.

¹H-NMR (CD₃OD, 400 MHz): δ 8.66 (1H, d, J=9.0 Hz), 8.33 (1H, s), 7.97 (2H, d, J=8.3 Hz), 7.92 (1H, d, J=2.2 Hz), 7.89 (1H, s), 7.74 (2H, d, J=8.0 Hz), 7.61 (1H, dd, J=2.4 Hz, J=8.8 Hz), 7.27 (1H, d, J=8.0 Hz), 3.77 (2H, s), 3.64 (2H, t, J=6.2 Hz), 2.67 (2H, t, J=6.3 Hz), 2.63 (2H, q, J=7.1 Hz), 2.38 (3H, s), 1.10 (3H, t, 7.2 Hz)

Mass spectrometric value (ESI-MS) 491 (M−1)

Compound 436 N-[4-Chloro-2-(3,4-dimethyl-benzylidene-hydrazinocarbonyl)-phenyl]-4-{[ethyl-(2-hydroxy-ethyl)-amino]-methyl}-benzamide

The title compound 436 was produced in the same manner as in Example 5.

¹H-NMR (CD₃OD, 400 MHz): δ 8.66 (1H, d, J=8.8 Hz), 8.30 (1H, s), 7.97 (2H, d, J=8.3 Hz), 7.92 (1H, d, J=2.4 Hz), 7.52-7.68 (5H, m), 7.20 (1H, d, J=7.8 Hz), 3.77 (2H, s), 3.64 (2H, t, J=6.2 Hz), 2.67 (2H, t, J=6.2 Hz), 2.63 (2H, q, J=7.2 Hz), 2.32 (3H, s), 2.31 (3H, s), 1.10 (3H, t, J=7.1 Hz)

Mass spectrometric value (ESI-MS) 505 (M−1)

Compound 437 N-[4-Chloro-2-(4-chloro-3-trifluoromethyl-benzylidene-hydrazinocarbonyl)-phenyl]-4-{[ethyl-(2-hydroxy-ethyl)-amino]-methyl}-benzamide

The title compound 437 was produced in the same manner as in Example 5.

¹H-NMR (CD₃OD, 400 MHz): δ 8.64 (1H, d, J=9.0 Hz), 8.39 (1H, s), 8.34 (1H, s), 8.05 (1H, d, J=8.1 Hz), 7.93-7.98 (2H, m), 7.89 (1H, s), 7.70 (1H, d, J=8.3 Hz), 7.63 (1H, dd, J=2.4 Hz, J=9.0 Hz), 7.56 (2H, d, J=8.3 Hz), 3.75 (2H, s), 3.63 (2H, t, J=6.4 Hz), 2.64 (2H, t, J=6.4 Hz), 2.60 (2H, q, J=7.1 Hz), 1.09 (3H, t, J=7.2 Hz)

Mass spectrometric value (ESI-MS) 579 (M−1)

Compound 438 N-[4-Chloro-2-(3-methoxy-benzylidene-hydrazinocarbonyl)-phenyl]-4-{[ethyl-(2-hydroxy-ethyl)-amino]-methyl}-benzamide

The title compound 438 was produced in the same manner as in Example 5.

¹H-NMR (CD₃OD, 400 MHz): δ 8.66 (1H, d, J=8.8 Hz), 8.33 (1H, s), 7.92-7.99 (3H, m), 7.62 (1H, dd, J=2.2 Hz, J=8.8 Hz), 7.54-7.60 (3H, m), 7.28-7.37 (2H, m), 6.98-7.04 (1H, m), 3.87 (3H, s), 3.74 (2H, s), 3.63 (2H, t, J=6.2 Hz), 2.64 (2H, t, J=6.3 Hz), 2.60 (2H, q, J=7.2 Hz), 1.09 (3H, t, J=7.1 Hz)

Mass spectrometric value (ESI-MS) 507 (M−1)

Compound 439 N-[4-Chloro-2-(4-methoxy-benzylidene-hydrazinocarbonyl)-phenyl]-4-{[ethyl-(2-hydroxy-ethyl)-amino]-methyl}-benzamide

The title compound 439 was produced in the same manner as in Example 5.

¹H-NMR (CD₃OD, 400 MHz): δ 8.66 (1H, d, J=9.0 Hz), 8.31 (1H, s), 7.96 (2H, d, J=8.3 Hz), 7.92 (1H, d, J=2.4 Hz), 7.80 (2H, d, J=8.8 Hz), 7.61 (1H, dd, J=2.4 Hz, J=9.0 Hz), 7.56 (2H, d, J=8.3 Hz), 6.99 (2H, d, J=8.8 Hz), 3.85 (3H, s), 3.74 (2H, s), 3.63 (2H, t, J=6.4 Hz), 2.65 (2H, t, J=6.4 Hz), 2.60 (2H, q, J=7.2 Hz), 1.09 (3H, t, J=7.1 Hz)

Mass spectrometric value (ESI-MS) 507 (M−1)

Compound 440 N-[4-Chloro-2-(3-hydroxy-benzylidene-hydrazinocarbonyl)-phenyl]-4-{[ethyl-(2-hydroxy-ethyl)-amino]-methyl}-benzamide

The title compound 440 was produced in the same manner as in Example 5.

¹H-NMR (CD₃OD, 400 MHz): δ 8.65 (1H, d, J=8.8 Hz), 8.29 (1H, s), 7.88-7.99 (3H, m), 7.62 (1H, dd, J=2.4 Hz, J=9.0 Hz), 7.56 (2H, d, J=8.3 Hz), 7.30-7.33 (1H, m), 7.23-7.27 (2H, m), 6.85-6.91 (1H, m), 3.75 (2H, s), 3.63 (2H, t, J=6.3 Hz), 2.65 (2H, t, J=6.2 Hz), 2.61 (2H, q, J=7.1 Hz), 1.09 (3H, t, J=7.1 Hz)

Mass spectrometric value (ESI-MS) 493 (M−1)

Compound 441 N-[4-Chloro-2-(4-hydroxy-benzylidene-hydrazinocarbonyl)-phenyl]-4-{[ethyl-(2-hydroxy-ethyl)-amino]-methyl}-benzamide

The title compound 441 was produced in the same manner as in Example 5.

¹H-NMR (CD₃OD, 400 MHz): δ 8.66 (1H, d, J=8.8 Hz), 8.27 (1H, s), 7.97 (2H, d, J=8.1 Hz), 7.91 (1H, d, J=2.4 Hz), 7.70 (2H, d, J=8.8 Hz), 7.61 (1H, dd, J=2.4 Hz, J=9.0 Hz), 7.56 (2H, d, J=8.3 Hz), 6.85 (2H, d, J=8.8 Hz), 3.78 (2H, s), 3.64 (2H, t, J=6.2 Hz), 2.68 (2H, t, J=6.2 Hz), 2.64 (2H, q, J=7.2 Hz), 1.10 (3H, t, J=7.1 Hz)

Mass spectrometric value (ESI-MS) 493 (M−1)

Compound 442 N-[4-Chloro-2-(3-fluoro-benzylidene-hydrazinocarbonyl)-phenyl]-4-(2-diethylamino-ethylsulfanylmethyl)-benzamide

The title compound 442 was produced in the same manner as in Example 5.

¹H-NMR (CD₃OD, 400 MHz): δ 8.65 (1H, d, J=9.0 Hz), 8.36 (1H, s), 7.97 (2H, d, J=8.3 Hz), 7.94 (1H, d, J=2.4 Hz), 7.71 (1H, d, J=8.1 Hz), 7.58-7.65 (2H, m), 7.55 (2H, d, J=8.3 Hz), 7.43-7.50 (1H, m), 7.15-7.25 (1H, m), 3.85 (2H, s), 2.60-2.67 (2H, m), 2.50-2.59 (6H, m), 1.00 (6H, t, J=7.2 Hz)

Mass spectrometric value (ESI-MS) 539 (M−1)

Compound 443 N-[4-Chloro-2-(4-fluoro-benzylidene-hydrazinocarbonyl)-phenyl]-4-(2-diethylamino-ethylsulfanylmethyl)-benzamide

The title compound 443 was produced in the same manner as in Example 5.

¹H-NMR (CD₃OD, 400 MHz): δ 8.65 (1H, d, J=9.0 Hz), 8.35 (1H, s), 7.97 (2H, d, J=8.3 Hz), 7.88-7.95 (3H, m), 7.62 (1H, dd, J=2.2 Hz, J=8.8 Hz), 7.55 (1H, d, J=8.3 Hz), 7.19 (2H, dd, J=8.7 Hz, J=8.7 Hz), 3.85 (1H, s), 2.49-2.67 (8H, m), 1.00 (6H, t, J=7.2 Hz)

Mass spectrometric value (ESI-MS) 539 (M−1)

Compound 444 N-[4-Chloro-2-(3-methyl-benzylidene-hydrazinocarbonyl)-phenyl]-4-(2-diethylamino-ethylsulfanylmethyl)-benzamide

The title compound 444 was produced in the same manner as in Example 5.

¹H-NMR (CD₃OD, 400 MHz): δ 8.66 (1H, d, J=8.8 Hz), 8.33 (1H, s), 7.97 (2H, d, J=8.3 Hz), 7.93 (1H, d, J=2.4 Hz), 7.72 (1H, s), 7.60-7.65 (2H, m), 7.55 (2H, d, J=8.3 Hz), 7.25-7.36 (2H, m), 3.84 (2H, s), 2.48-2.66 (8H, m), 2.39 (3H, s), 1.00 (6H, t, J=7.2 Hz)

Mass spectrometric value (ESI-MS) 535 (M−1)

Compound 445 N-[4-Chloro-2-(4-methyl-benzylidene-hydrazinocarbonyl)-phenyl]-4-(2-diethylamino-ethylsulfanylmethyl)-benzamide

The title compound 445 was produced in the same manner as in Example 5.

¹H-NMR (CD₃OD, 400 MHz): δ 8.66 (1H, d, J=8.8 Hz), 8.33 (1H, s), 7.97 (2H, d, J=8.3 Hz), 7.93 (1H, d, J=2.4 Hz), 7.74 (2H, d, J=7.8 Hz), 7.61 (1H, dd, J=2.2 Hz, J=9.0 Hz), 7.55 (2H, d, J=8.3 Hz), 7.27 (2H, d, J=7.8 Hz), 3.84 (2H, s), 2.47-2.66 (8H, m), 2.39 (3H, s), 1.00 (6H, t, J=7.2 Hz)

Mass spectrometric value (ESI-MS) 535 (M−1)

Compound 446 N-[4-Chloro-2-(3,4-dimethyl-benzylidene-hydrazinocarbonyl)-phenyl]-4-(2-diethylamino-ethylsulfanylmethyl)-benzamide

The title compound 446 was produced in the same manner as in Example 5.

¹H-NMR (CD₃OD, 400 MHz): δ 8.66 (1H, d, J=9.0 Hz), 8.33 (1H, s), 7.96 (2H, d, J=8.3 Hz), 7.91 (1H, d, J=2.4 Hz), 7.65 (1H, s), 7.60 (1H, dd, J=2.4 Hz, J=9.0 Hz), 7.51-7.56 (3H, m), 7.19 (1H, d, J=7.8 Hz), 3.83 (2H, s), 2.58-2.65 (2H, m), 2.48-2.58 (6H, m), 2.31 (3H, s), 2.29 (3H, s), 0.99 (6H, t, J=7.2 Hz)

Mass spectrometric value (ESI-MS) 549 (M−1)

Compound 447 N-[4-Chloro-2-(4-chloro-3-trifluoromethyl-benzylidene-hydrazinocarbonyl)-phenyl]-4-(2-diethylamino-ethylsulfanylmethyl)-benzamide

The title compound 447 was produced in the same manner as in Example 5.

¹H-NMR (CD₃OD, 400 MHz): δ 8.64 (1H, d, J=9.0 Hz), 8.39 (1H, s), 8.35 (1H, s), 8.05 (1H, d, J=8.3 Hz), 7.93-7.99 (3H, m), 7.70 (1H, d, J=8.3 Hz), 7.63 (1H, dd, J=2.4 Hz, J=9.0 Hz), 7.55 (2H, d, J=8.0 Hz), 3.85 (2H, s), 2.50-2.68 (8H, m), 1.00 (6H, t, J=7.2 Hz)

Mass spectrometric value (ESI-MS) 623 (M−1)

Compound 448 N-[4-Chloro-2-(3-methoxy-benzylidene-hydrazinocarbonyl)-phenyl]-4-(2-diethylamino-ethylsulfanylmethyl)-benzamide

The title compound 448 was produced in the same manner as in Example 5.

¹H-NMR (CD₃OD, 400 MHz): δ 8.66 (1H, d, J=9.0 Hz), 8.33 (1H, s), 7.92-8.00 (3H, m), 7.63 (1H, dd, J=2.4 Hz, J=9.0 Hz), 7.59 (1H, s), 7.55 (2H, d, J=8.0 Hz), 7.28-7.38 (2H, m), 6.98-7.03 (1H, m), 3.88 (3H, s), 3.84 (2H, s), 2.58-2.66 (2H, m), 2.47-2.58 (6H, m), 0.99 (6H, t, J=7.2 Hz)

Mass spectrometric value (ESI-MS) 551 (M−1)

Compound 449 N-[4-Chloro-2-(4-methoxy-benzylidene-hydrazinocarbonyl)-phenyl]-4-(2-diethylamino-ethylsulfanylmethyl)-benzamide

The title compound 449 was produced in the same manner as in Example 5.

¹H-NMR (CD₃OD, 400 MHz): δ 8.66 (1H, d, J=9.0 Hz), 8.31 (1H, s), 7.97 (2H, d, J=8.3 Hz), 7.92 (1H, d, J=2.4 Hz), 7.80 (2H, d, J=8.8 Hz), 7.61 (1H, dd, J=2.4 Hz, J=9.0 Hz), 7.55 (2H, d, J=8.6 Hz), 7.00 (2H, d, J=8.8 Hz), 3.85 (3H, s), 3.84 (2H, s), 2.49-2.67 (8H, m), 1.00 (6H, t, J=7.2 Hz)

Mass spectrometric value (ESI-MS) 551 (M−1)

Compound 450 N-[4-Chloro-2-(3-hydroxy-benzylidene-hydrazinocarbonyl)-phenyl]-4-(2-diethylamino-ethylsulfanylmethyl)-benzamide

The title compound 450 was produced in the same manner as in Example 5.

¹H-NMR (CD₃OD, 400 MHz): δ 8.64 (1H, d, J=9.0 Hz), 8.29 (1H, s), 7.97 (2H, d, J=8.3 Hz), 7.93 (1H, d, J=2.4 Hz), 7.62 (1H, dd, J=2.4 Hz, J=8.8 Hz), 7.55 (2H, d, J=8.3 Hz), 7.31 (1H, s), 7.22-7.28 (2H, m), 6.83-6.91 (1H, m), 3.85 (2H, s), 2.57-2.66 (2H, m), 2.48-2.57 (6H, m), 1.00 (6H, t, J=7.2 Hz)

Mass spectrometric value (ESI-MS) 537 (M−1)

Compound 451 N-[4-Chloro-2-(4-hydroxy-benzyl idene-hydrazinocarbonyl)-phenyl]-4-(2-diethylamino-ethylsulfanylmethyl)-benzamide

The title compound 451 was produced in the same manner as in Example 5.

¹H-NMR (CD₃OD, 400 MHz): δ 8.66 (1H, d, J=8.8 Hz), 8.27 (1H, s), 7.96 (2H, d, J=8.3 Hz), 7.91 (1H, d, J=2.4 Hz), 7.71 (2H, d, J=8.6 Hz), 7.61 (1H, dd, J=2.4 Hz, J=9.0 Hz), 7.55 (2H, d, J=8.3 Hz), 6.84 (2H, d, J=8.8 Hz), 3.84 (2H, s), 2.49-2.66 (8H, m), 1.00 (6H, t, J=7.2 Hz)

Mass spectrometric value (ESI-MS) 537 (M−1)

Compound 452 N-[4-Chloro-2-(3-fluoro-benzylidene-hydrazinocarbonyl)-phenyl]-3-(2-diethylamino-ethylsulfanylmethyl)-benzamide

The title compound 452 was produced in the same manner as in Example 5.

¹H-NMR (CD₃OD, 400 MHz): δ 8.65 (1H, d, J=9.0 Hz), 8.36 (1H, s), 7.93-7.99 (2H, m), 7.89 (1H, d, J=8.3 Hz), 7.70 (1H, d, J=8.5 Hz), 7.52-7.65 (3H, m), 7.41-7.56 (2H, m), 7.15-7.23 (1H, m), 3.88 (2H, s), 2.42-2.66 (8H, m), 0.96 (6H, t, J=7.2 Hz)

Mass spectrometric value (ESI-MS) 539 (M−1)

Compound 453 N-[4-Chloro-2-(4-fluoro-benzylidene-hydrazinocarbonyl)-phenyl]-3-(2-diethylamino-ethylsulfanylmethyl)-benzamide

The title compound 453 was produced in the same manner as in Example 5.

¹H-NMR (CD₃OD, 400 MHz): δ 8.65 (1H, d, J=8.8 Hz), 8.36 (1H, s), 7.85-7.99 (5H, m), 7.57-7.65 (2H, m), 7.47-7.55 (1H, m), 7.12-7.23 (2H, m), 3.88 (2H, s), 2.46-2.65 (8H, m), 0.96 (6H, t, J=7.2 Hz)

Mass spectrometric value (ESI-MS) 539 (M−1)

Compound 454 N-[4-Chloro-2-(3-methyl-benzylidene-hydrazinocarbonyl)-phenyl]-3-(2-diethylamino-ethylsulfanylmethyl)-benzamide

The title compound 454 was produced in the same manner as in Example 5.

¹H-NMR (CD₃OD, 400 MHz): δ 8.66 (1H, d, J=9.0 Hz), 8.34 (1H, s), 7.98 (1H, s), 7.89 (1H, d, J=7.1 Hz), 7.71 (1H, s), 7.59-7.66 (3H, m), 7.52 (1H, dd, J=7.7 Hz, J=7.7 Hz), 7.24-7.35 (2H, m), 3.88 (2H, s), 2.46-2.65 (8H, m), 2.39 (3H, s), 0.96 (6H, t, J=7.2 Hz)

Mass spectrometric value (ESI-MS) 535 (M−1)

Compound 455 N-[4-Chloro-2-(4-methyl-benzylidene-hydrazinocarbonyl)-phenyl]-3-(2-diethylamino-ethylsulfanylmethyl)-benzamide

The title compound 455 was produced in the same manner as in Example 5.

¹H-NMR (CD₃OD, 400 MHz): δ 8.65 (1H, d, J=9.0 Hz), 8.33 (1H, s), 7.97 (1H, s), 7.84-7.95 (2H, m), 7.73 (2H, d, J=8.1 Hz), 7.58-7.65 (2H, m), 7.51 (1H, dd, J=7.6 Hz, J=7.6 Hz), 7.26 (2H, d, J=7.8 Hz), 3.88 (2H, s), 2.46-2.66 (8H, m), 2.38 (3H, s), 0.96 (6H, t, J=7.2 Hz)

Mass spectrometric value (ESI-MS) 535 (M−1)

Compound 456 N-[4-Chloro-2-(3,4-dimethyl-benzylidene-hydrazinocarbonyl)-phenyl]-3-(2-diethylamino-ethylsulfanylmethyl)-benzamide

The title compound 456 was produced in the same manner as in Example 5.

¹H-NMR (CD₃OD, 400 MHz): δ 8.65 (1H, d, J=9.0 Hz), 8.30 (1H, s), 7.97 (1H, s), 7.87-7.94 (2H, m), 7.58-7.67 (3H, m), 7.48-7.56 (2H, m), 7.19 (1H, d, J=7.6 Hz), 3.88 (2H, s), 2.46-2.67 (8H, m), 2.31 (3H, s), 2.29 (3H, s), 0.96 (6H, q, J=7.2 Hz)

Mass spectrometric value (ESI-MS) 549 (M−1)

Compound 457 N-[4-Chloro-2-(4-chloro-3-trifluoromethyl-benzylidene-hydrazinocarbonyl)-phenyl]-3-(2-diethylamino-ethylsulfanylmethyl)-benzamide

The title compound 457 was produced in the same manner as in Example 5.

¹H-NMR (CD₃OD, 400 MHz): δ 8.63 (1H, d, J=9.0 Hz), 8.40 (1H, s), 8.33 (1H, s), 8.04 (1H, d, J=7.8 Hz), 7.93-8.00 (2H, m), 7.89 (1H, d, J=7.1 Hz), 7.69 (1H, d, J=8.0 Hz), 7.60-7.65 (2H, m), 7.52 (1H, dd, J=7.6 Hz, J=7.6 Hz), 3.88 (2H, s), 2.58-2.67 (2H, m), 2.47-2.58 (6H, m), 0.97 (6H, t, J=7.1 Hz)

Mass spectrometric value (ESI-MS) 623 (M−1)

Compound 458 N-[4-Chloro-2-(3-methoxy-benzylidene-hydrazinocarbonyl)-phenyl]-3-(2-diethylamino-ethylsulfanylmethyl)-benzamide

The title compound 458 was produced in the same manner as in Example 5.

¹H-NMR (CD₃OD, 400 MHz): δ 8.64 (1H, d, J=9.0 Hz), 8.34 (1H, s), 7.97 (1H, s), 7.93 (1H, d, J=2.4 Hz), 7.87-7.91 (1H, m), 7.59-7.65 (2H, m), 7.57 (1H, s), 7.51 (1H, dd, J=7.7 Hz, J=7.7 Hz), 7.28-7.37 (2H, m), 6.97-7.03 (1H, m), 3.87 (2H, s), 3.86 (3H, s), 2.46-2.65 (8H, m), 0.96 (6H, t, J=7.2 Hz)

Mass spectrometric value (ESI-MS) 551 (M−1)

Compound 459 N-[4-Chloro-2-(4-methoxy-benzylidene-hydrazinocarbonyl)-phenyl]-3-(2-diethylamino-ethylsulfanylmethyl)-benzamide

The title compound 459 was produced in the same manner as in Example 5.

¹H-NMR (CD₃OD, 400 MHz): δ 8.65 (1H, d, J=9.0 Hz), 8.31 (1H, s), 7.97 (1H, s), 7.92 (1H, d, J=2.4 Hz), 7.89 (1H, d, J=9.0 Hz), 7.79 (2H, d, J=8.8 Hz), 7.59-7.65 (2H, m), 7.51 (1H, dd, J=7.7 Hz, J=7.7 Hz), 6.99 (2H, d, J=8.8 Hz), 3.88 (2H, s), 3.84 (3H, s), 2.46-2.66 (8H, m), 0.96 (6H, t, J=7.2 Hz)

Mass spectrometric value (ESI-MS) 551 (M−1)

Compound 460 N-[4-Chloro-2-(3-hydroxy-benzylidene-hydrazinocarbonyl)-phenyl]-3-(2-diethylamino-ethylsulfanylmethyl)-benzamide

The title compound 460 was produced in the same manner as in Example 5.

Mass spectrometric value (ESI-MS) 537 (M−1)

Compound 461 N-[4-Chloro-2-(4-hydroxy-benzylidene-hydrazinocarbonyl)-phenyl]-3-(2-diethylamino-ethylsulfanylmethyl)-benzamide

The title compound 461 was produced in the same manner as in Example 5.

¹H-NMR (CD₃OD, 400 MHz): δ 8.66 (1H, d, J=9.0 Hz), 8.27 (1H, s), 7.97 (1H, s), 7.91 (1H, d, J=2.4 Hz), 7.89 (1H, d, J=7.6 Hz), 7.70 (2H, d, J=8.5 Hz), 7.58-7.65 (2H, m), 7.52 (1H, dd, J=7.8 Hz, J=7.8 Hz), 6.84 (2H, d, J=8.6 Hz), 3.88 (2H, s), 2.46-2.65 (8H, m), 0.96 (6H, t, J=7.2 Hz)

Mass spectrometric value (ESI-MS) 537 (M−1)

Compound 462 N-[4-Chloro-2-(3-fluoro-benzylidene-hydrazinocarbonyl)-phenyl]-3-[1-(2-dimethylamino-ethyl)-1H-tetrazol-5-ylsulfanylmethyl]-benzamide

The title compound 462 was produced in the same manner as in Example 5.

¹H-NMR (CD₃OD, 400 MHz): δ 8.62 (1H, d, J=9.0 Hz), 8.36 (1H, s), 8.03 (1H, s), 7.93 (1H, d, J=2.2 Hz), 7.88-7.93 (2H, m), 7.69 (1H, d, J=10.0 Hz), 7.58-7.65 (3H, m), 7.42-7.52 (2H, m), 7.19 (1H, ddd, J=2.0 Hz, J=8.4 Hz, J=8.4 Hz), 4.63 (2H, s), 4.33 (2H, t, J=6.3 Hz), 2.67 (2H, t, J=6.3 Hz), 2.18 (6H, s)

Mass spectrometric value (ESI-MS) 579, 581 (M−1)

Compound 463 N-[4-Chloro-2-(4-fluoro-benzylidene-hydrazinocarbonyl)-phenyl]-3-[1-(2-dimethylamino-ethyl)-1H-tetrazol-5-ylsulfanylmethyl]-benzamide

The title compound 463 was produced in the same manner as in Example 5.

¹H-NMR (CD₃OD, 400 MHz): δ 8.62 (1H, d, J=8.8 Hz), 8.36 (1H, s), 8.04 (1H, s), 7.87-7.94 (4H, m), 7.59-7.65 (2H, m), 7.48 (1H, dd, J=7.7 Hz, J=7.7 Hz), 7.19 (2H, dd, J=8.7 Hz, J=8.7 Hz), 4.63 (2H, s), 4.32 (2H, t, J=6.3 Hz), 2.67 (2H, t, J=6.3 Hz), 2.18 (6H, s)

Mass spectrometric value (ESI-MS) 579 (M−1)

Compound 464 N-[4-Chloro-2-(3-methyl-benzylidene-hydrazinocarbonyl)-phenyl]-3-[1-(2-dimethylamino-ethyl)-1H-tetrazol-5-ylsulfanylmethyl]-benzamide

The title compound 464 was produced in the same manner as in Example 5.

¹H-NMR (CD₃OD, 400 MHz): δ 8.63 (1H, d, J=9.0 Hz), 8.34 (1H, s), 8.04 (1H, s), 7.88-7.94 (2H, m), 7.70 (1H, s), 7.59-7.64 (3H, m), 7.49 (1H, dd, J=7.7 Hz, J=7.7 Hz), 7.25-7.36 (2H, m), 4.63 (2H, s), 4.32 (2H, s), 2.66 (2H, t, J=6.4 Hz), 2.39 (3H, s), 2.17 (6H, s)

Mass spectrometric value (ESI-MS) 575 (M−1)

Compound 465 N-[4-Chloro-2-(4-methyl-benzylidene-hydrazinocarbonyl)-phenyl]-3-[1-(2-dimethylamino-ethyl)-1H-tetrazol-5-ylsulfanylmethyl]-benzamide

The title compound 465 was produced in the same manner as in Example 5.

¹H-NMR (CD₃OD, 400 MHz): δ 8.63 (1H, d, J=8.8 Hz), 8.33 (1H, s), 8.04 (1H, s), 7.88-7.94 (2H, m), 7.73 (2H, d, J=8.1 Hz), 7.61 (2H, dd, J=2.2 Hz, J=9.0 Hz), 7.48 (1H, dd, J=7.7 Hz, J=7.7 Hz), 7.27 (2H, d, J=8.1 Hz), 4.63 (2H, s), 4.32 (2H, t, J=6.3 Hz), 2.67 (2H, t, J=6.3 Hz), 2.38 (3H, s), 2.17 (6H, s)

Mass spectrometric value (ESI-MS) 575 (M−1)

Compound 466 N-[4-Chloro-2-(3,4-dimethyl-benzylidene-hydrazinocarbonyl)-phenyl]-3-[1-(2-dimethylamino-ethyl)-1H-tetrazol-5-ylsulfanylmethyl]-benzamide

The title compound 466 was produced in the same manner as in Example 5.

¹H-NMR (CD₃OD, 400 MHz): δ 8.63 (1H, d, J=8.8 Hz), 8.30 (1H, s), 8.04 (1H, s), 7.89-7.95 (2H, m), 7.59-7.68 (3H, m), 7.54 (1H, d, J=8.0 Hz), 7.49 (1H, dd, J=7.7 Hz, J=7.7 Hz), 7.21 (1H, d), 4.63 (2H, s), 4.32 (2H, t, J=6.3 Hz), 2.66 (2H, t, J=6.3 Hz), 2.32 (3H, s), 2.31 (3H, s), 2.17 (6H, s)

Mass spectrometric value (ESI-MS) 589, 591 (M−1)

Compound 467 N-[4-Chloro-2-(4-chloro-3-trifluoromethyl-benzylidene-hydrazinocarbonyl)-phenyl]-3-[1-(2-dimethylamino-ethyl)-1H-tetrazol-5-ylsulfanylmethyl]-benzamide

The title compound 467 was produced in the same manner as in Example 5.

¹H-NMR (CD₃OD, 400 MHz): δ 8.60 (1H, d, J=9.0 Hz), 8.39 (1H, s), 8.31 (1H, s), 8.02-8.07 (2H, m), 7.93 (1H, d, J=2.2 Hz), 7.89 (1H, d, J=7.8 Hz), 7.69 (1H, d, J=8.3 Hz), 7.62 (2H, dd, J=2.2 Hz, J=8.8 Hz), 7.49 (1H, dd, J=7.7 Hz, J=7.7 Hz), 4.63 (2H, s), 4.32 (2H, t, J=6.4 Hz), 3.44 (1H, s), 2.67 (2H, t, J=6.3 Hz), 2.18 (6H, s)

Mass spectrometric value (ESI-MS) 663 (M−1)

Compound 468 N-[4-Chloro-2-(3-methoxy-benzylidene-hydrazinocarbonyl)-phenyl]-3-[1-(2-dimethylamino-ethyl)-1H-tetrazol-5-ylsulfanylmethyl]-benzamide

The title compound 468 was produced in the same manner as in Example 5.

¹H-NMR (CD₃OD, 400 MHz): δ 8.63 (1H, d, J=9.0 Hz), 8.34 (1H, s), 8.04 (1H, s), 7.94 (1H, d, J=2.4 Hz), 7.91 (1H, d, J=8.3 Hz), 7.60-7.66 (2H, m), 7.57 (1H, s), 7.49 (1H, dd, J=7.8 Hz, J=7.8 Hz), 7.28-7.38 (2H, m), 6.98-7.04 (1H, m), 4.63 (2H, s), 4.32 (2H, t, J=6.4 Hz), 3.86 (3H, s), 3.44 (1H, s), 2.67 (2H, t, J=6.3 Hz), 2.17 (6H, s)

Mass spectrometric value (ESI-MS) 591 (M−1)

Compound 469 N-[4-Chloro-2-(4-methoxy-benzylidene-hydrazinocarbonyl)-phenyl]-3-[1-(2-dimethylamino-ethyl)-1H-tetrazol-5-ylsulfanylmethyl]-benzamide

The title compound 469 was produced in the same manner as in Example 5.

¹H-NMR (CD₃OD, 400 MHz): δ 8.63 (1H, d, J=9.0 Hz), 8.31 (1H, s), 8.04 (1H, s), 7.88-7.94 (2H, m), 7.79 (2H, d, J=8.8 Hz), 7.58-7.64 (2H, m), 7.48 (1H, dd, J=7.7 Hz, J=7.7 Hz), 6.99 (2H, d, J=8.8 Hz), 4.63 (2H, s), 4.32 (2H, t, J=6.3 Hz), 3.84 (3H, s), 3.45 (1H, s), 2.67 (2H, t, J=6.3 Hz), 2.18 (6H, s)

Mass spectrometric value (ESI-MS) 591 (M−1)

Compound 470 N-[4-Chloro-2-(3-hydroxy-benzylidene-hydrazinocarbonyl)-phenyl]-3-[1-(2-dimethylamino-ethyl)-1H-tetrazol-5-ylsulfanylmethyl]-benzamide

The title compound 470 was produced in the same manner as in Example 5.

¹H-NMR (CD₃OD, 400 MHz): δ 8.62 (1H, d, J=8.8 Hz), 8.29 (1H, s), 8.04 (1H, s), 7.89-7.95 (2H, m), 7.55-7.65 (2H, m), 7.48 (1H, dd, J=7.8 Hz, J=7.8 Hz), 7.31 (1H, s), 7.22-7.29 (2H, m), 6.86-6.90 (1H, m), 4.63 (2H, s), 4.32 (2H, s), 2.67 (2H, t, J=6.3 Hz), 2.17 (6H, s)

Mass spectrometric value (ESI-MS) 577 (M−1)

Compound 471 N-[4-Chloro-2-(4-hydroxy-benzylidene-hydrazinocarbonyl)-phenyl]-3-[1-(2-dimethylamino-ethyl)-1H-tetrazol-5-ylsulfanylmethyl]-benzamide

The title compound 471 was produced in the same manner as in Example 5.

¹H-NMR (CD₃OD, 400 MHz): δ 8.63 (1H, d, J=9.0 Hz), 8.27 (1H, s), 8.04 (1H, s), 7.87-7.93 (2H, m), 7.69 (2H, d, J=8.5 Hz), 7.57-7.63 (2H, m), 7.48 (1H, dd, J=77 Hz, J=7.7 Hz), 6.84 (2H, d, J=8.5 Hz), 4.63 (2H, s), 4.32 (2H, t, J=6.4 Hz), 2.67 (2H, t, J=6.4 Hz), 2.17 (6H, s)

Mass spectrometric value (ESI-MS) 577 (M−1)

Compound 472 3-{[(2-Diethylamino-ethyl)-methyl-amino]-methyl}-N-[2-(3-fluoro-benzylidene-hydrazinocarbonyl)-4-iodo-phenyl]-benzamide

The title compound 472 was produced in the same manner as in Example 5.

¹H-NMR (CD₃OD, 400 MHz): δ 8.44 (1H, d, J=8.8 Hz), 8.36 (1H, s), 8.23 (1H, s), 7.97 (1H, s), 7.88-7.95 (2H, m), 7.68 (1H, d, J=9.5 Hz), 7.42-7.63 (5H, m), 7.18 (1H, dd, J=8.4 Hz, J=8.4 Hz), 3.67 (2H, s), 2.78 (2H, t, J=7.1 Hz), 2.65 (4H, q, J=7.2 Hz), 2.58 (2H, t, J=7.2 Hz), 2.28 (3H, s), 1.04 (6H, t, J=7.2 Hz)

Mass spectrometric value (ESI-MS) 628 (M−1)

Compound 473 3-{[(2-Diethylamino-ethyl)-methyl-amino]-methyl}-N-[2-(4-fluoro-benzylidene-hydrazinocarbonyl)-4-iodo-phenyl]-benzamide

The title compound 473 was produced in the same manner as in Example 5.

¹H-NMR (CD₃OD, 400 MHz): δ 8.44 (1H, d, J=8.8 Hz), 8.36 (1H, s), 8.21 (1H, d, J=1.9 Hz), 7.86-7.99 (5H, m), 7.60 (1H, d, J=7.6 Hz), 7.52 (1H, dd, J=8.8 Hz, J=8.8 Hz), 7.18 (2H, dd, J=8.8 Hz, J=8.8 Hz), 3.67 (2H, s), 2.77 (2H, t, J=7.1 Hz), 2.64 (4H, q, J=7.2 Hz), 2.58 (2H, t, J=7.2 Hz), 2.28 (3H, s), 1.04 (6H, t, J=7.2 Hz)

Mass spectrometric value (ESI-MS) 628 (M−1)

Compound 474 3-{[(2-Di ethylamino-ethyl)-methyl-amino]-methyl}-N-[4-iodo-2-(3-methyl-benzylidene-hydrazinocarbonyl)-phenyl]-benzamide

The title compound 474 was produced in the same manner as in Example 5.

¹H-NMR (CD₃OD, 400 MHz): δ 8.45 (1H, d, J=8.8 Hz), 8.33 (1H, s), 8.22 (1H, d, J=1.1 Hz), 7.97 (1H, s), 7.88-7.93 (2H, m), 7.69 (1H, s), 7.58-7.63 (2H, m), 7.52 (1H, dd, J=7.7 Hz, J=7.7 Hz), 7.32 (1H, dd, J=7.6 Hz, J=7.6 Hz), 7.25 (1H, d, J=7.3 Hz), 3.66 (2H, s), 2.67-2.73 (2H, m), 2.52-2.61 (6H, m), 2.38 (3H, s), 2.27 (3H, s), 1.01 (6H, t, J=7.2 Hz)

Mass spectrometric value (ESI-MS) 624 (M−1)

Compound 475 3-{[(2-Diethylamino-ethyl)-methyl-amino]-methyl}-N-[4-iodo-2-(4-methyl-benzylidene-hydrazinocarbonyl)-phenyl]-benzamide

The title compound 475 was produced in the same manner as in Example 5.

¹H-NMR (CD₃OD, 400 MHz): δ 8.44 (1H, d, J=8.8 Hz), 8.33 (1H, s), 8.21 (1H, d, J=2.0 Hz), 7.97 (1H, s), 7.89-7.94 (2H, m), 7.72 (2H, d, J=8.0 Hz), 7.60 (1H, d, J=7.6 Hz), 7.52 (1H, dd, J=7.7 Hz, J=7.7 Hz), 7.26 (2H, d, J=7.8 Hz), 3.67 (2H, s), 2.75 (2H, t, J=7.2 Hz), 2.62 (4H, q, J=7.2 Hz), 2.57 (2H, t, J=7.2 Hz), 2.37 (3H, s), 2.28 (3H, s), 1.03 (6H, t, J=7.2 Hz)

Mass spectrometric value (ESI-MS) 624 (M−1)

Compound 476 3-{[(2-Diethylamino-ethyl)-methyl-amino]-methyl}-N42-(3,4-dimethyl-benzylidene-hydrazinocarbonyl)-4-iodo-phenyl]-benzamide

The title compound 476 was produced in the same manner as in Example 5.

¹H-NMR (CD₃OD, 400 MHz): δ 8.44 (1H, d, J=8.8 Hz), 8.30 (1H, s), 8.20 (1H, d, J=2.0 Hz), 7.97 (1H, s), 7.90 (2H, dd, J=2.0 Hz, J=8.8 Hz), 7.58-7.66 (2H, m), 7.48-7.56 (2H, m), 7.19 (1H, d, J=7.8 Hz), 3.66 (2H, s), 2.68-2.75 (2H, m), 2.53-2.64 (6H, m), 2.30 (3H, s), 2.29 (3H, s), 2.27 (3H, s), 1.02 (6H, t, J=7.2 Hz)

Mass spectrometric value (ESI-MS) 638 (M−1)

Compound 477 N-[2-(4-chloro-3-trifluoromethyl-benzylidene-hydrazinocarbonyl)-4-iodo-phenyl]-3-{[(2-diethylamino-ethyl)-methyl-amino]-methyl}-benzamide

The title compound 477 was produced in the same manner as in Example 5.

¹H-NMR (CD₃OD, 400 MHz): δ 8.43 (1H, d, J=8.8 Hz), 8.38 (1H, s), 8.32 (1H, s), 8.25 (1H, s), 8.02 (1H, d, J=0.6 Hz), 7.97 (1H, s), 7.88-7.94 (2H, m), 7.67 (1H, d, J=8.5 Hz), 7.60 (1H, d, J=7.3 Hz), 7.52 (1H, dd, J=7.6 Hz, J=7.6 Hz), 3.66 (2H, s), 2.75 (2H, t, J=7.2 Hz), 2.62 (4H, q, J=7.2 Hz), 2.56 (2H, t, J=7.2 Hz), 2.27 (3H, s), 1.03 (6H, t, J=7.2 Hz)

Mass spectrometric value (ESI-MS) 712 (M−1)

Compound 478 3-{[(2-Diethylamino-ethyl)-methyl-amino]-methyl}-N-[4-iodo-2-(3-methoxy-benzylidene-hydrazinocarbonyl)-phenyl]-benzamide

The title compound 478 was produced in the same manner as in Example 5.

¹H-NMR (CD₃OD, 400 MHz): δ 8.44 (1H, d, J=8.8 Hz), 8.33 (1H, s), 8.22 (1H, d, J=2.0 Hz), 7.97 (1H, s), 7.88-7.94 (2H, m), 7.60 (1H, d, J=7.6 Hz), 7.56 (1H, bs), 7.52 (1H, dd, J=7.7 Hz, J=7.7 Hz), 7.22-7.36 (2H, m), 6.97-7.03 (1H, m), 3.86 (3H, s), 3.66 (2H, s), 2.71 (2H, t, J=7.2 Hz), 2.53-2.62 (6H, m), 2.27 (3H, s), 1.02 (6H, t, J=7.2 Hz)

Mass spectrometric value (ESI-MS) 640 (M−1)

Compound 479 3-{[(2-Diethylamino-ethyl)-methyl-amino]-methyl}-N-[4-iodo-2-(4-methoxy-benzylidene-hydrazinocarbonyl)-phenyl]-benzamide

The title compound 479 was produced in the same manner as in Example 5.

¹H-NMR (CD₃OD, 400 MHz): δ 8.45 (1H, d, J=8.8 Hz), 8.31 (1H, s), 8.20 (1H, d, J=2.2 Hz), 7.97 (1H, s), 7.88-7.94 (2H, m), 7.78 (2H, d, J=8.8 Hz), 7.60 (1H, d, J=7.6 Hz), 7.52 (1H, dd, J=7.7 Hz, J=7.7 Hz), 6.99 (2H, d, J=8.8 Hz), 3.84 (3H, s), 3.67 (2H, s), 2.73 (2H, t, J=7.2 Hz), 2.60 (4H, q, J=7.2 Hz), 2.54-2.60 (2H, m), 2.28 (3H, s), 1.03 (6H, t, J=7.2 Hz)

Mass spectrometric value (ESI-MS) 640 (M−1)

Compound 480 3-{[(2-Diethylamino-ethyl)-methyl-amino]-methyl}-N-[2-(3-hydroxy-benzylidene-hydrazinocarbonyl)-4-iodo-phenyl]-benzamide

The title compound 480 was produced in the same manner as in Example 5.

¹H-NMR (CD₃OD, 400 MHz): δ 8.44 (1H, d, J=8.8 Hz), 8.29 (1H, s), 8.21 (1H, d, J=2.0 Hz), 7.97 (1H, s), 7.88-7.94 (2H, m), 7.60 (1H, d, J=7.6 Hz), 7.52 (1H, dd, J=7.6 Hz, J=7.6 Hz), 7.30 (1H, s), 7.20-7.28 (2H, m), 6.87 (1H, ddd, J=2.2 Hz, J=2.2 Hz, J=7.1 Hz), 3.66 (2H, s), 2.72 (2H, t, J=7.2 Hz), 2.59 (4H, q, J=7.2 Hz), 2.56 (2H, t, J=6.8 Hz), 2.27 (3H, s), 1.02 (6H, t, J=7.2 Hz)

Mass spectrometric value (ESI-MS) 626 (M−1)

Compound 481 3-{[(2-Diethylamino-ethyl)-methyl-amino]-methyl}-N-[2-(4-hydroxy-benzylidene-hydrazinocarbonyl)-4-iodo-phenyl]-benzamide

The title compound 481 was produced in the same manner as in Example 5.

¹H-NMR (CD₃OD, 400 MHz): δ 8.45 (1H, d, J=8.8 Hz), 8.27 (1H, s), 8.19 (1H, d, J=2.0 Hz), 7.97 (1H, s), 7.88-7.95 (2H, m), 7.69 (1H, d, J=8.5 Hz), 7.52 (1H, dd, J=7.7 Hz, J=7.7 Hz), 6.83 (2H, d, J=8.5 Hz), 3.67 (2H, s), 2.75 (2H, t, J=7.2 Hz), 2.62 (4H, q, J=7.2 Hz), 2.75-2.64 (2H, m), 2.28 (3H, s), 1.03 (6H, t, J=7.2 Hz)

Mass spectrometric value (ESI-MS) 626 (M−1)

Compound 482 3-[1,4′]Bipiperidinyl-1′-ylmethyl-N-[2-(3-fluoro-benzylidene-hydrazinocarbonyl)-4-iodo-phenyl]-benzamide

The title compound 482 was produced in the same manner as in Example 5.

¹H-NMR (CD₃OD, 400 MHz): δ 8.44 (1H, d, J=8.8 Hz), 8.36 (1H, s), 8.22 (1H, d, J=2.0 Hz), 7.87-7.97 (4H, m), 7.42-7.72 (4H, m), 7.14-7.23 (1H, m), 3.61 (2H, s), 2.98 (2H, d, J=11.5 Hz), 2.60 (4H, bs), 2.30-2.40 (1H, m), 2.05 (2H, t, J=11.2 Hz), 1.82-1.91 (2H, m), 1.55-1.66 (6H, m), 1.40-1.50 (2H, m)

Mass spectrometric value (ESI-MS) 666 (M−1)

Compound 483 3-[1,4′]Bipiperidinyl-1′-ylmethyl-N-[2-(4-fluoro-benzylidene-hydrazinocarbonyl)-4-iodo-phenyl]-benzamide

The title compound 483 was produced in the same manner as in Example 5.

¹H-NMR (CD₃OD, 400 MHz): δ 8.43 (1H, d, J=8.8 Hz), 8.35 (1H, s), 8.21 (1H, d, J=2.0 Hz), 7.85-7.97 (5H, m), 7.58 (1H, d, J=7.8 Hz), 7.51 (1H, dd, J=7.7 Hz, J=7.7 Hz), 7.18 (2H, dd, J=8.7 Hz, J=8.7 Hz), 3.61 (2H, s), 2.98 (2H, d, J=12.0 Hz), 2.59 (4H, bs), 2.25-2.38 (1H, m), 2.05 (2H, t, J=11.5 Hz), 1.85 (2H, d, J=12.7 Hz), 1.54-1.66 (6H, m), 1.40-1.50 (2H, m)

Mass spectrometric value (ESI-MS) 666 (M−1)

Compound 484 3-[1,4′]Bipiperidinyl-1′-ylmethyl-N-[4-iodo-2-(3-methyl-benzylidene-hydrazinocarbonyl)-phenyl]-benzamide

The title compound 484 was produced in the same manner as in Example 5.

¹H-NMR (CD₃OD, 400 MHz): δ 8.44 (1H, d, J=8.8 Hz), 8.34 (1H, s), 8.21 (1H, d, J=1.9 Hz), 7.88-7.97 (3H, m), 7.68 (1H, s), 7.55-7.64 (2H, m), 7.50 (1H, dd, J=7.7 Hz, J=7.7 Hz), 7.21-7.34 (2H, m), 3.60 (2H, s), 2.97 (2H, d, J=10.8 Hz), 2.54 (4H, bs), 2.38 (3H, s), 2.25-2.35 (1H, m), 2.25-2.35 (1H, m), 2.03 (2H, t, J=11.7 Hz), 1.83 (2H, d, J=12.4 Hz), 1.50-1.65 (6H, m), 1.38-1.48 (2H, m)

Mass spectrometric value (ESI-MS) 662 (M−1)

Compound 485 3-[1,4′]Bipiperidinyl-1′-ylmethyl-N-[4-iodo-2-(4-methyl-benzylidene-hydrazinocarbonyl)-phenyl]-benzamide

The title compound 485 was produced in the same manner as in Example 5.

¹H-NMR (CD₃OD, 400 MHz): δ 8.44 (1H, d, J=8.8 Hz), 8.33 (1H, s), 8.21 (1H, d, J=2.0 Hz), 7.87-7.97 (3H, m), 7.72 (2H, d, J=8.1 Hz), 7.58 (1H, d, J=7.6 Hz), 7.51 (1H, dd, J=7.6 Hz, J=7.6 Hz), 7.26 (2H, d, J=8.1 Hz), 3.61 (2H, s), 2.98 (2H, d, J=11.0 Hz), 2.55 (4H, bs), 2.37 (3H, s), 2.23-2.35 (1H, m), 2.05 (2H, t, J=11.7 Hz), 1.84 (2H, d, J=12.0 Hz), 1.53-1.66 (6H, m), 1.40-1.50 (2H, m)

Mass spectrometric value (ESI-MS) 662 (M−1)

Compound 486 3-[1,4′]Bipiperidinyl-1′-ylmethyl-N-[2-(3,4-dimethyl-benzylidene-hydrazinocarbonyl)-4-iodo-phenyl]-benzamide

The title compound 486 was produced in the same manner as in Example 5.

¹H-NMR (CD₃OD, 400 MHz): δ 8.44 (1H, d, J=8.8 Hz), 8.30 (1H, s), 8.19 (1H, d, J=2.2 Hz), 7.87-7.96 (3H, m), 7.62 (1H, s), 7.57 (1H, d, J=7.6 Hz), 7.51 (2H, d, J=7.6 Hz), 7.15-7.22 (1H, m), 3.60 (2H, s), 2.92-3.02 (2H, m), 2.52 (4H, bs), 2.29 (3H, s), 2.27 (3H, s), 2.20-2.33 (1H, m), 1.98-2.09 (2H, m), 1.78-2.87 (2H, m), 1.50-1.65 (6H, m), 1.38-1.48 (2H, m)

Mass spectrometric value (ESI-MS) 676 (M−1)

Compound 487 3-[1,4′]Bipiperidinyl-1′-ylmethyl-N-[2-(4-chloro-3-trifluoromethyl-benzylidene-hydrazinocarbonyl)-4-iodo-phenyl]-benzamide

The title compound 487 was produced in the same manner as in Example 5.

¹H-NMR (CD₃OD, 400 MHz): δ 8.38-8.45 (2H, m), 8.24 (1H, s), 8.24 (1H, s), 8.03 (1H, d, J=8.0 Hz), 7.87-7.97 (3H, m), 7.68 (1H, d, J=8.3 Hz), 7.58 (1H, d, J=6.8 Hz), 7.51 (1H, dd, J=7.7 Hz, J=7.7 Hz), 3.61 (2H, s), 2.98 (2H, d, J=10.5 Hz), 2.59 (4H, s), 2.28-2.38 (1H, m), 2.04 (2H, t, J=11.7 Hz), 1.80-1.90 (2H, m98, 1.55-1.65 (6H, m), 1.41-1.50 (2H, m)

Mass spectrometric value (ESI-MS) 750 (M−1)

Compound 488 3-[1,4′]Bipiperidinyl-t-ylmethyl-N-[4-iodo-2-(3-methoxy-benzylidene-hydrazinocarbonyl)-phenyl]-benzamide

The title compound 488 was produced in the same manner as in Example 5.

¹H-NMR (CD₃OD, 400 MHz): δ 8.44 (1H, d, J=8.8 Hz), 8.34 (1H, s), 8.21 (1H, d, J=2.0 Hz), 7.87-7.97 (3H, m), 7.48-7.60 (3H, m), 7.27-7.36 (2H, m), 6.96-7.03 (1H, m), 3.85 (3H, s), 3.60 (2H, s), 2.97 (2H, d, J=11.2 Hz), 2.55 (4H, bs), 2.23-2.33 (1H, m), 2.03 (2H, t, J=11.6 Hz), 1.83 (2H, d, J=11.2 Hz), 1.53-1.65 (6H, m), 1.40-1.50 (2H, m)

Mass spectrometric value (ESI-MS) 678 (M−1)

Compound 489 3-[1,4′]Bipiperidinyl-t-ylmethyl-N-[4-iodo-2-(4-methoxy-benzylidene-hydrazinocarbonyl)-phenyl]-benzamide

The title compound 489 was produced in the same manner as in Example 5.

¹H-NMR (CD₃OD, 400 MHz): δ 8.44 (1H, d, J=8.8 Hz), 8.32 (1H, s), 8.18-8.22 (1H, m), 7.87-7.97 (3H, m), 7.75-7.82 (2H, m), 7.55-7.62 (1H, m), 7.45-7.55 (1H, m), 6.95-7.03 (2H, m), 3.84 (3H, s), 3.61 (2H, s), 2.93-3.02 (21-1, m), 2.56 (4H, bs), 2.20-2.35 (1H, m), 2.00-2.10 (2H, m), 1.80-1.88 (2H, m), 1.55-1.65 (6H, m), 1.40-1.50 (2H, m)

Mass spectrometric value (ESI-MS) 678 (M−1)

Compound 490 3-[1,4′]Bipiperidinyl-1′-ylmethyl-N-[2-(3-hydroxy-benzylidene-hydrazinocarbonyl)-4-iodo-phenyl]-benzamide

The title compound 490 was produced in the same manner as in Example 5.

¹H-NMR (CD₃OD, 400 MHz): δ 8.43 (1H, d, J=8.8 Hz), 8.29 (1H, s), 8.19-8.22 (1H, m), 7.87-7.97 (3H, m), 7.57 (1H, d, J=7.3 Hz), 7.47-7.53 (1H, m), 7.30 (1H, s), 7.18-7.27 (2H, m), 6.83-6.89 (1H, m), 3.61 (2H, s), 2.98 (2H, d, J=10.5 Hz), 2.56 (4H, bs), 2.25-2.35 (1H, m), 2.04 (2H, t, J=12.0 Hz), 1.84 (2H, d, J=12.0 Hz), 1.53-1.66 (6H, m), 1.40-1.50 (2H, m)

Mass spectrometric value (ESI-MS) 664 (M−1)

Compound 491 3-[1,4′]Bipiperidinyl-1′-ylmethyl-N-[2-(4-hydroxy-benzylidene-hydrazinocarbonyl)-4-iodo-phenyl]-benzamide

The title compound 491 was produced in the same manner as in Example 5.

¹H-NMR (CD₃OD, 400 MHz): δ 8.44 (1H, dd, J=3.7 Hz, J=8.8 Hz), 8.27 (1H, s), 8.18 (1H, bs), 7.86-7.96 (3H, m), 7.65-7.72 (2H, m), 7.54-7.61 (1H, m), 7.47-7.54 (1H, m), 6.79-6.86 (2H, m), 3.59-3.64 (2H, m), 2.93-3.03 (4H, m), 2.57 (4H, bs), 2.25-2.37 (1H, m), 1.95-2.10 (2H, m), 1.80-1.90 (2H, m), 1.58 (6H, bs), 1.45 (2H, bs)

Mass spectrometric value (ESI-MS) 664 (M−1)

Compound 492 N-{4-Chloro-2-[N′-(3,4-dimethyl-benzyl)-hydrazinocarbonyl]-phenyl}-3-(2-hydroxy-ethylsulfanylmethyl)-benzamide

The title compound 492 was produced in the same manner as in Example 5.

¹H-NMR (CD₃OD, 400 MHz): δ 8.60 (1H, d, J=8.8 Hz), 7.90 (1H, s), 7.78 (1H, d, J=7.6 Hz), 7.59-7.70 (2H, m), 7.45-7.55 (2H, m), 7.09-7.13 (2H, m), 7.01 (1H, d, J=7.8 Hz), 3.96 (2H, s), 3.86 (2H, s), 3.67 (2H, t, J=6.8 Hz), 2.58 (2H, t, J=6.8 Hz), 2.16 (3H, s), 2.09 (3H, s)

Mass spectrometric value (ESI-MS) 496, 498, 499 (M−1)

Compound 493 N-[4-Chloro-2-(3,4-dimethyl-benzylidene-hydrazinocarbonyl)-phenyl]-3-(2-hydroxy-ethanesulfonylmethyl)-benzamide

The title compound 493 was produced in the same manner as in Example 6.

¹H-NMR (CD₃OD, 400 MHz): δ 8.67 (1H, d, J=9.0 Hz), 8.31 (1H, s), 8.11 (1H, s), 8.04 (1H, d, J=8.0 Hz), 7.94 (1H, d, J=2.4 Hz), 7.73 (1H, d, J=8.0 Hz), 7.67 (1H, s), 7.58-7.64 (2H, m), 7.54 (1H, d, J=7.3 Hz), 7.21 (1H, d, J=7.6 Hz), 4.63 (2H, s), 4.06 (2H, t, J=5.6 Hz), 3.20 (2H, t, J=5.7 Hz), 2.32 (3H, s), 2.32 (3H, s)

Mass spectrometric value (ESI-MS) 526, 528, 529 (M−1)

Compound 494 N-[4-Bromo-2-(4-methyl-benzylidene-hydrazinocarbonyl)-phenyl]-4-methyl-benzamide

The title compound 494 was produced in the same manner as in Example 5.

¹H-NMR (CDCl₃, 400 MHz): δ 8.52 (1H, d, J=8.8 Hz), 8.33 (1H, s), 7.93 (2H, d, J=7.8 Hz), 7.65-7.74 (3H, m), 7.54 (1H, d, J=8.5 Hz), 7.21-7.30 (4H, m), 2.24 (3H, s), 2.38 (3H, s)

Mass spectrometric value (ESI-MS) 448, 450 (M−1)

Compound 495 Pyridin-2-carboxylic acid[4-bromo-2-(3-fluoro-benzylidene-hydrazinocarbonyl)-phenyl]-amide

The title compound 495 was produced in the same manner as in Example 5.

¹H-NMR (CDCl₃, 400 MHz): δ 8.72 (1H, s), 8.67 (1H, d, J=9.0 Hz), 8.28 (1H, s), 8.22 (1H, d, J=7.8 Hz), 7.86-7.92 (2H, m), 7.66 (1H, dd, J=2.2 Hz, J=8.8 Hz), 7.51-7.60 (2H, m), 7.46-7.51 (1H, m), 7.33-7.39 (1H, m), 7.03-7.10 (1H, m)

Mass spectrometric value (ESI-MS) 439, 441 (M−1)

Compound 496 Pyridin-2-carboxylic acid [4-bromo-2-(4-fluoro-benzylidene-hydrazinocarbonyl)-phenyl]-amide

The title compound 496 was produced in the same manner as in Example 5.

¹H-NMR (CDCl₃, 400 MHz): δ 8.70 (1H, d, J=4.1 Hz), 8.65 (1H, d, J=9.0 Hz), 8.29 (1H, s), 8.21 (1H, d, J=7.8 Hz), 7.84-7.91 (2H, m), 7.74-7.81 (2H, m), 7.61-7.66 (1H, m), 7.44-7.50 (1H, m), 7.06 (2H, dd, J=8.5 Hz, J=8.5 Hz)

Mass spectrometric value (ESI-MS) 439, 441 (M−1)

Compound 497 Pyridin-2-carboxylic acid [4-bromo-2-(3-methyl-benzylidene-hydrazinocarbonyl)-phenyl]-amide

The title compound 497 was produced in the same manner as in Example 5.

¹H-NMR (CDCl₃, 400 MHz): δ 8.69 (1H, s), 8.65 (1H, d, J=9.0 Hz), 8.29 (1H, s), 8.22 (1H, d, J=7.8 Hz), 7.79-7.89 (2H, m), 7.57-7.66 (2H, m), 7.48-7.54 (1H, m), 7.41-7.46 (1H, m), 7.21-7.27 (1H, m), 7.11-7.17 (1H, m), 2.35 (3H, s)

Mass spectrometric value (ESI-MS) 435, 437 (M−1)

Compound 498 Pyridin-2-carboxylic acid [4-bromo-2-(4-methyl-benzylidene-hydrazinocarbonyl)-phenyl]-amide

The title compound 498 was produced in the same manner as in Example 5.

¹H-NMR (CDCl₃, 400 MHz): δ 8.63 (1H, d, J=3.9 Hz), 8.58 (1H, d, J=9.0 Hz), 8.24 (1H, s), 8.16 (1H, d, J=8.1 Hz), 7.77-7.84 (2H, m), 7.52-7.62 (3H, m), 7.37-7.42 (1H, m), 7.11 (2H, d, J=8.1 Hz), 2.25 (3H, s)

Mass spectrometric value (ESI-MS) 435, 437 (M−1)

Compound 499 Pyridin-2-carboxylic acid [4-bromo-2-(3,4-dimethyl-benzylidene-hydrazinocarbonyl)-phenyl]-amide

The title compound 499 was produced in the same manner as in Example 5.

¹H-NMR (CDCl₃, 400 MHz): δ 8.69 (1H, s), 8.65 (1H, d, J=9.0 Hz), 8.24 (1H, s), 8.21 (1H, d, J=7.8 Hz), 7.80-7.89 (2H, m), 7.57-7.63 (2H, m), 7.42-7.47 (2H, m), 7.12 (1H, d, J=7.6 Hz), 2.26 (3H, s), 2.21 (3H, s)

Mass spectrometric value (ESI-MS) 449, 451 (M−1)

Compound 500 Pyridin-2-carboxylic acid [4-bromo-2-(4-chloro-3-trifluoromethyl-benzylidene-hydrazinocarbonyl)-phenyl]amide

The title compound 500 was produced in the same manner as in Example 5.

¹H-NMR (CDCl₃, 400 MHz): δ 8.63 (1H, s), 8.59 (1H, d, J=8.8 Hz), 8.24 (1H, s), 8.14 (1H, d, J=7.8 Hz), 7.97 (1H, s), 7.92 (1H, d, J=7.8 Hz), 7.78-7.84 (2H, m), 7.58 (1H, dd, J=2.2 Hz, J=9.0 Hz), 7.45 (1H, d, J=8.3 Hz), 7.38-7.43 (1H, m)

Mass spectrometric value (ESI-MS) 523, 525 (M−1)

Compound 501 N-[4-Bromo-2-(3-fluoro-benzylidene-hydrazinocarbonyl)-phenyl]-4-ethoxy-benzamide

The title compound 501 was produced in the same manner as in Example 5.

¹H-NMR (CDCl₃, 400 MHz): δ 8.52 (1H, d, J=8.8 Hz), 8.35 (1H, s), 7.99 (2H, d, J=8.5 Hz), 7.71 (1H, s), 7.51-7.60 (3H, m), 7.35-7.42 (1H, m), 7.09-7.15 (1H, m), 6.95-6.99 (2H, m), 4.10 (2H, q, J=7.0 Hz), 1.45 (3H, t, J=7.0 Hz)

Mass spectrometric value (ESI-MS) 482, 484 (M−1)

Compound 502 N-[4-Bromo-2-(4-fluoro-benzylidene-hydrazinocarbonyl)-phenyl]-4-ethoxy-benzamide

The title compound 502 was produced in the same manner as in Example 5.

¹H-NMR (CDCl₃, 400 MHz): δ 8.53 (1H, d, J=9.0 Hz), 8.25 (1H, s), 7.92 (2H, d, J=8.8 Hz), 7.70-7.79 (3H, m), 7.55 (1H, dd, J=9.0 Hz, J=2.2 Hz), 7.00-7.09 (2H, m), 6.87-6.94 (2H, m), 4.04 (2H, q, J=7.0 Hz), 1.39 (3H, t, J=7.0 Hz)

Mass spectrometric value (ESI-MS) 482, 484 (M−1)

Compound 503 N-[4-Bromo-2-(4-methyl-benzylidene-hydrazinocarbonyl)-phenyl]-4-ethoxy-benzamide

The title compound 503 was produced in the same manner as in Example 5.

¹H-NMR (CDCl₃, 400 MHz): δ 8.56 (1H, d, J=9.0 Hz), 8.31 (1H, s), 7.99 (2H, d, J=8.5 Hz), 7.71 (2H, s), 7.69 (1H, s), 7.53-7.59 (1H, m), 7.22 (2H, d, J=8.1 Hz), 6.96 (2H, d, J=8.8 Hz), 4.09 (2H, q, J=7.0 Hz), 2.38 (3H, s), 1.44 (3H, t, J=7.0 Hz)

Mass spectrometric value (ESI-MS) 478, 480 (M−1)

Compound 504 N-[4-Bromo-2-(3,4-dimethyl-benzylidene-hydrazinocarbonyl)-phenyl]-4-ethoxy-benzamide

The title compound 504 was produced in the same manner as in Example 5.

¹H-NMR (CDCl₃, 400 MHz): δ 8.48 (1H, d, J=8.5 Hz), 8.33 (1H, s), 7.99 (2H, d, J=8.1 Hz), 7.69 (1H, s), 7.63 (1H, s), 7.45-7.56 (2H, m), 7.16 (1H, d, J=7.8 Hz), 6.92-6.98 (2H, m), 4.08 (2H, q, J=6.9 Hz), 2.29 (3H, s), 2.27 (3H, s), 1.44 (3H, t, J=6.8 Hz)

Mass spectrometric value (ESI-MS) 492, 494 (M−1)

Compound 505 Pyridin-2-carboxylic acid [2-(3-fluoro-benzylidene-hydrazinocarbonyl)-phenyl]-amide

The title compound 505 was produced in the same manner as in Example 5.

¹H-NMR (CDCl₃, 400 MHz): δ 8.65-8.76 (2H, m), 8.20-8.28 (2H, m), 7.86-7.92 (1H, m), 7.65-7.72 (1H, m), 7.50-7.61 (3H, m), 7.43-7.50 (1H, m), 7.31-7.38 (1H, m), 7.10-7.20 (1H, m), 7.02-7.10 (1H, m)

Mass spectrometric value (ESI-MS) 361 (M−1)

Compound 506 Pyridin-2-carboxylic acid [2-(4-fluoro-benzylidene-hydrazinocarbonyl)-phenyl]-amide

The title compound 506 was produced in the same manner as in Example 5.

¹H-NMR (CDCl₃, 400 MHz): δ 8.65-8.75 (2H, m), 8.20-8.28 (2H, m), 7.88 (1H, dd, J=1.7 Hz, J=7.7 Hz), 7.74-7.83 (2H, m), 7.63-7.70 (1H, m), 7.51-7.59 (1H, m), 7.43-7.49 (1H, m), 7.09-7.19 (1H, m), 7.06 (2H, dd, J=8.5 Hz, J=8.5 Hz)

Mass spectrometric value (ESI-MS) 361 (M−1)

Compound 507 Pyridin-2-carboxylic acid [2-(3,4-dimethyl-benzylidene-hydrazinocarbonyl)-phenyl]-amide

The title compound 507 was produced in the same manner as in Example 5.

¹H-NMR (CDCl₃, 400 MHz): δ 8.65-8.74 (2H, m), 8.23 (1H, d, J=7.6 Hz), 8.20 (1H, s), 7.87 (1H, ddd, J=1.7 Hz, J=7.7 Hz, J=7.7 Hz), 7.63-7.69 (1H, m), 7.57-7.63 (1H, m), 7.49-7.57 (1H, m), 7.42-7.49 (2H, m), 7.07-7.15 (2H, m), 2.26 (3H, s), 2.24 (3H, s)

Mass spectrometric value (ESI-MS) 371 (M−1)

Compound 508 Pyridin-2-carboxylic acid [2-(4-chloro-3-trifluoromethyl-benzylidene-hydrazinocarbonyl)-phenyl]-amide

The title compound 508 was produced in the same manner as in Example 5.

¹H-NMR (CDCl₃, 400 MHz): δ 8.67-8.73 (2H, m), 8.29 (1H, s), 8.23 (1H, d, J=7.8 Hz), 7.96-8.05 (2H, m), 7.89 (1H, ddd, J=1.7 Hz, J=7.7 Hz, J=7.7 Hz), 7.70 (1H, d, J=7.1 Hz), 7.46-7.59 (3H, m), 7.11-7.18 (1H, m)

Mass spectrometric value (ESI-MS) 445 (M−1)

Compound 509 Cyclohexanecarboxylic acid [4-bromo-2-(3-fluoro-benzylidene-hydrazinocarbonyl)-phenyl]-amide

The title compound 509 was produced in the same manner as in Example 5.

¹H-NMR (CDCl₃, 400 MHz): δ 8.49 (1H, d, J=9.0 Hz), 8.22-8.29 (1H, m), 7.48-7.68 (3H, m), 7.35-7.44 (2H, m), 7.12-7.18 (1H, m), 2.27-2.36 (1H, m), 1.97-2.04 (2H, m), 1.79-1.87 (2H, m), 1.66-1.73 (1H, m), 1.45-1.52 (1H, m), 1.21-1.38 (4H, m)

Mass spectrometric value (ESI-MS) 444, 446 (M−1)

Compound 510 Isoxazole-5-carboxylic acid [4-bromo-2-(3-fluoro-benzylidene-hydrazinocarbonyl)-phenyl]-amide

The title compound 510 was produced in the same manner as in Example 5.

¹H-NMR (CDCl₃, 400 MHz): δ 8.59 (1H, d, J=8.8 Hz), 8.39 (1H, d, J=2.0 Hz), 8.31 (1H, s), 7.92 (1H, s), 7.63 (1H, dd, J=2.2 Hz, J=9.0 Hz), 7.51-7.59 (2H, m), 7.34-7.41 (1H, m), 7.07-7.13 (1H, m), 7.03 (1H, d, J=1.7 Hz)

Mass spectrometric value (ESI-MS) 429, 431 (M−1)

Compound 511 Isoxazole-5-carboxylic acid [4-bromo-2-(3-methyl-benzylidene-hydrazinocarbonyl)-phenyl]-amide

The title compound 511 was produced in the same manner as in Example 5.

¹H-NMR (CDCl₃, 400 MHz): δ 8.58 (1H, d, J=9.0 Hz), 8.39 (1H, d, J=2.0 Hz), 8.29 (1H, s), 7.93 (1H, d, J=1.7 Hz), 7.63-7.70 (2H, m), 7.55 (1H, d, J=7.8 Hz), 7.17-7.31 (2H, m), 7.03 (1H, d, J=1.7 Hz), 2.38 (3H, s)

Mass spectrometric value (ESI-MS) 425, 427 (M−1)

Compound 512 Isoxazole-5-carboxylic acid [4-bromo-2-(3,4-dimethyl-benzylidene-hydrazinocarbonyl)-phenyl]-amide

The title compound 512 was produced in the same manner as in Example 5.

¹H-NMR (CDCl₃, 400 MHz): δ 8.59 (1H, d, J=8.8 Hz), 8.40 (1H, d, J=1.7 Hz), 8.26 (1H, s), 7.96 (1H, d, J=2.2 Hz), 7.68 (1H, dd, J=2.2 Hz, J=9.0 Hz), 7.63 (1H, s), 7.51 (1H, d, J=7.3 Hz), 7.18 (1H, d, J=7.8 Hz), 7.05 (1H, d, J=1.7 Hz), 2.30 (3H, s), 2.29 (3H, s)

Mass spectrometric value (ESI-MS) 439, 441 (M−1)

Compound 513 Isoxazole-5-carboxylic acid [4-bromo-2-(4-chloro-3-trifluoromethyl-benzylidene-hydrazinocarbonyl)-phenyl]-amide

The title compound 513 was produced in the same manner as in Example 5.

¹H-NMR (CDCl₃, 400 MHz): δ 8.60 (1H, d, J=9.0 Hz), 8.42 (1H, d, J=1.7 Hz), 8.35 (1H, s), 8.10 (1H, s), 8.04 (1H, d, J=8.3 Hz), 7.97-8.01 (1H, m), 7.70 (1H, dd, J=2.3 Hz, J=8.9 Hz), 7.58 (1H, d, J=8.3 Hz), 7.06 (1H, d, J=1.7 Hz)

Mass spectrometric value (ESI-MS) 513, 515 (M−1)

Compound 514 2,5-Dimethyl-furan-3-carboxylic acid [2-(3-fluoro-benzylidene-hydrazinocarbonyl)-phenyl]-amide

The title compound 514 was produced in the same manner as in Example 5.

¹H-NMR (CDCl₃, 400 MHz): δ 8.56 (1H, d, J=8.5 Hz), 8.27 (1H, s), 7.46-7.68 (4H, m), 7.35-7.42 (1H, m), 7.04-7.14 (2H, m), 6.39 (1H, s), 2.62 (3H, s), 2.29 (3H, s)

Mass spectrometric value (ESI-MS) 378 (M−1)

Compound 515 2,5-Dimethyl-furan-3-carboxylic acid [2-(4-fluoro-benzylidene-hydrazinocarbonyl)-phenyl]-amide

The title compound 515 was produced in the same manner as in Example 5.

¹H-NMR (CDCl₃, 400 MHz): δ 8.54 (1H, d, J=8.3 Hz), 8.27 (1H, s), 7.76-7.85 (2H, m), 7.61 (1H, d, J=7.6 Hz), 7.48 (1H, t, J=7.8 Hz), 7.01-7.16 (3H, m), 6.38 (1H, s), 2.62 (3H, s), 2.28 (3H, s)

Mass spectrometric value (ESI-MS) 378 (M−1)

Compound 516 2,5-Dimethyl-furan-3-carboxylic acid [2-(3-methyl-benzylidene-hydrazinocarbonyl)-phenyl]-amide

The title compound 516 was produced in the same manner as in Example 5.

¹H-NMR (CDCl₃, 400 MHz): δ 8.56 (1H, d, J=8.1 Hz), 8.27 (1H, s), 7.67-7.74 (1H, m), 7.40-7.60 (4H, m), 7.28-7.35 (1H, m), 6.96-7.04 (1H, m), 6.38 (1H, s), 2.64 (3H, s), 2.40 (3H, s), 2.29 (3H, s)

Mass spectrometric value (ESI-MS) 374 (M−1)

Compound 517 N-[3-(3-Fluoro-benzylidene-hydrazinocarbonyl)-4-methyl-thiophen-2-yl]-3,4-dimethoxy-benzamide

The title compound 517 was produced in the same manner as in Example 5.

¹H-NMR (CDCl₃, 400 MHz): δ 8.15 (1H, s), 7.62-7.69 (2H, m), 7.58 (1H, d, J=9.3 Hz), 7.52 (1H, d, J=7.6 Hz), 7.37-7.44 (1H, m), 7.10-7.17 (1H, m), 6.93 (1H, d, J=8.3 Hz), 6.53 (1H, s), 3.98 (3H, s), 3.96 (3H, s), 2.60 (3H, s)

Mass spectrometric value (ESI-MS) 440 (M−1)

Compound 518 3,4-Dimethoxy-N-[4-methyl-3-(3-methyl-benzylidene-hydrazinocarbonyl)-thiophen-2-yl]-benzamide

The title compound 518 was produced in the same manner as in Example 5.

¹H-NMR (CDCl₃, 400 MHz): δ 8.10 (1H, s), 7.63-7.72 (3H, m), 7.54 (1H, d, J=7.6 Hz), 7.24-7.35 (2H, m), 6.92 (1H, d, J=8.3 Hz), 6.53 (1H, s), 3.98 (3H, s), 3.96 (3H, s), 2.61 (3H, s), 2.40 (3H, s)

Mass spectrometric value (ESI-MS) 436 (M−1)

Compound 519 3,4-Dimethoxy-N-[4-methyl-3-(4-methyl-benzylidene-hydrazinocarbonyl)-thiophen-2-yl]-benzamide

The title compound 519 was produced in the same manner as in Example 5.

¹H-NMR (CDCl₃, 400 MHz): δ 8.10 (1H, s), 7.63-7.73 (4H, m), 7.22-7.28 (2H, m), 6.92 (1H, d, J=8.1 Hz), 6.54 (1H, s), 3.98 (3H, s), 3.96 (3H, s), 2.61 (3H, s), 2.40 (3H, s)

Mass spectrometric value (ESI-MS) 436 (M−1)

Compound 521 N-[3-(3,4-Dimethyl-benzylidene-hydrazinocarbonyl)-4-methyl-thiophen-2-yl]-3,4-dimethoxy-benzamide

The title compound 521 was produced in the same manner as in Example 5.

¹H-NMR (CDCl₃, 400 MHz): δ 8.07 (1H, s), 7.63-7.70 (3H, m), 7.47 (1H, d, J=8.5 Hz), 7.19 (1H, d, J=7.8 Hz), 6.92 (1H, d, J=8.5 Hz), 6.54 (1H, s), 3.98 (3H, s), 3.96 (3H, s), 2.61 (3H, s), 2.31 (6H, s)

Mass spectrometric value (ESI-MS) 450 (M−1)

Compound 522 N-[3-(4-Chloro-3-trifluoromethyl-benzylidene-hydrazinocarbonyl)-4-methyl-thiophen-2-yl]-3,4-dimethoxy-benzamide

The title compound 522 was produced in the same manner as in Example 5.

¹H-NMR (CDCl₃, 400 MHz): δ 8.23 (1H, s), 8.05-8.08 (1H, m), 7.93-7.98 (1H, m), 7.62-7.68 (2H, m), 7.58 (1H, d, J=8.5 Hz), 6.92-7.68 (2H, m), 7.58 (1H, d, J=8.5 Hz), 6.92-6.97 (1H, m), 6.55 (1H, s), 3.98 (3H, s), 3.96 (3H, s), 2.61 (3H, s)

Mass spectrometric value (ESI-MS) 524 (M−1)

Compound 523 N-[2-(3,4-Dimethyl-benzylidene-hydrazinocarbonyl)-4-methyl-thiophen-3-yl]-3-(1H-[1,2,4]triazol-3-ylsulfanylmethyl)-benzamide

The title compound 523 was produced in the same manner as in Example 5.

Mass spectrometric value (ESI-MS) 503 (M−1)

Compound 524 N-[2-(3-Fluoro-benzylidene-hydrazinocarbonyl)-4-methyl-thiophen-3-yl]-3-(1H-[1,2,4]triazol-3-ylsulfanylmethyl)-benzamide

The title compound 524 was produced in the same manner as in Example 5.

Mass spectrometric value (ESI-MS) 493 (M−1)

Compound 525 N-[2-(3,4-Dimethyl-benzylidene-hydrazinocarbonyl)-4-methyl-thiophen-3-yl]-3-(3-hydroxy-propylsulfanylmethyl)-benzamide

The title compound 525 was produced in the same manner as in Example 5.

Mass spectrometric value (ESI-MS) 494 (M−1)

Compound 526 3-(3-Hydroxy-propylsulfanylmethyl)-N-[4-methyl-2-(4-methyl-benzylidene-hydrazinocarbonyl)-thiophen-3-yl]-benzamide

The title compound 526 was produced in the same manner as in Example 5.

Mass spectrometric value (ESI-MS) 480 (M−1)

Compound 527 N-[2-(3-Fluoro-benzylidene-hydrazinocarbonyl)-4-methyl-thiophen-3-yl]-3-(3-hydroxy-propylsulfanylmethyl)-benzamide

The title compound 527 was produced in the same manner as in Example 5.

Mass spectrometric value (ESI-MS) 484 (M−1)

Compound 528 3-{[(2-Diethylamino-ethyl)-methyl-amino]-methyl}-N-[2-(4-fluoro-benzylidene-hydrazinocarbonyl)-4-methyl-thiophen-3-yl]-benzamide

The title compound 528 was produced in the same manner as in Example 5.

Mass spectrometric value (ESI-MS) 522 (M−1)

Compound 529 3-{[(2-Diethylamino-ethyl)-methyl-amino]-methyl}-N-[2-(3-fluoro-benzylidene-hydrazinocarbonyl)-4-methyl-thiophen-3-yl]-benzamide

The title compound 529 was produced in the same manner as in Example 5.

Mass spectrometric value (ESI-MS) 522 (M−1)

Compound 530 3-{[(2-Diethylamino-ethyl)-methyl-amino]-methyl}-N-[2-(4-methoxy-benzylidene-hydrazinocarbonyl)-4-methyl-thiophen-3-yl]-benzamide

The title compound 530 was produced in the same manner as in Example 5.

Mass spectrometric value (ESI-MS) 534 (M−1)

Compound 531 3-[1,41′]Bipiperidinyl-1′-ylmethyl-N-[2-(4-methoxy-benzylidene-hydrazinocarbonyl)-4-methyl-thiophen-3-yl]-benzamide

The title compound 531 was produced in the same manner as in Example 5.

Mass spectrometric value (ESI-MS) 572 (M−1)

Compound 532 N-[2-(3,4-Dimethyl-benzylidene-hydrazinocarbonyl)-4-methyl-thiophen-3-yl]-3-[4-(2-hydroxy-ethyl)-piperazin-1-ylmethyl]-benzamide

The title compound 532 was produced in the same manner as in Example 5.

Mass spectrometric value (ESI-MS) 532 (M−1)

Compound 533 3-[4-(2-Hydroxy-ethyl)-piperazin-1-ylmethyl]-N-[4-methyl-2-(4-methyl-benzylidene-hydrazinocarbonyl)-thiophen-3-yl]-benzamide

The title compound 533 was produced in the same manner as in Example 5.

Mass spectrometric value (ESI-MS) 518 (M−1)

Compound 534 N-[2-(4-Fluoro-benzylidene-hydrazinocarbonyl)-4-methyl-thiophen-3-yl]-3-[4-(2-hydroxy-ethyl)-piperazin-1-ylmethyl]-benzamide

The title compound 534 was produced in the same manner as in Example 5.

Mass spectrometric value (ESI-MS) 522 (M−1)

Compound 535 N-[2-(3-Fluoro-benzylidene-hydrazinocarbonyl)-4-methyl-thiophen-3-yl]-3-[4-(2-hydroxy-ethyl)-piperazin-1-ylmethyl]-benzamide

The title compound 535 was produced in the same manner as in Example 5.

Mass spectrometric value (ESI-MS) 522 (M−1)

Compound 536 3-[(2-Diethylamino-ethylamino)-methyl]-N-[2-(3,4-dimethyl-benzylidene-hydrazinocarbonyl)-4-methyl-thiophen-3-yl]-benzamide

The title compound 536 was produced in the same manner as in Example 5.

Mass spectrometric value (ESI-MS) 518 (M−1)

Compound 537 3-[(2-Diethylamino-ethylamino)-methyl]-N-[4-methyl-2-(4-methyl-benzylidene-hydrazinocarbonyl)-thiophen-3-yl]-benzamide

The title compound 537 was produced in the same manner as in Example 5.

Mass spectrometric value (ESI-MS) 504 (M−1)

Compound 538 3-[(2-Diethylamino-ethylamino)-methyl]-N-[2-(3-fluoro-benzylidene-hydrazinocarbonyl)-4-methyl-thiophen-3-yl]-benzamide

The title compound 538 was produced in the same manner as in Example 5.

Mass spectrometric value (ESI-MS) 508 (M−1)

Compound 539 N-[2-(4-Chloro-3-trifluoromethyl-benzylidene-hydrazinocarbonyl)-4-methyl-thiophen-3-yl]-3-[(2-diethylamino-ethylamino)-methyl]-benzamide

The title compound 539 was produced in the same manner as in Example 5.

Mass spectrometric value (ESI-MS) 592 (M−1)

Compound 540 3-{[Bis-(2-hydroxy-propyl)-amino]-methyl}-N-[4-methyl-2-(4-methyl-benzylidene-hydrazinocarbonyl)-thiophen-3-yl]-benzamide

The title compound 540 was produced in the same manner as in Example 5.

Mass spectrometric value (ESI-MS) 521 (M−1)

Compound 541 N12-(3,4-Dimethyl-benzylidene-hydrazinocarbonyl)-4-methyl-thiophen-3-yl]-3-(4-hydroxy-piperidin-1-ylmethyl)-benzamide

The title compound 541 was produced in the same manner as in Example 5.

Mass spectrometric value (ESI-MS) 503 (M−1)

Compound 542 N-[2-(3-Fluoro-benzylidene-hydrazinocarbonyl)-4-methyl-thiophen-3-yl]-3-(4-hydroxy-piperidin-1-ylmethyl)-benzamide

The title compound 542 was produced in the same manner as in Example 5.

Mass spectrometric value (ESI-MS) 493 (M−1)

Compound 543 3-(4-Hydroxy-piperidin-1-ylmethyl)-N-[2-(4-methoxy-benzylidene-hydrazinocarbonyl)-4-methyl-thiophen-3-yl]-benzamide

The title compound 543 was produced in the same manner as in Example 5.

Mass spectrometric value (ESI-MS) 505 (M−1)

Compound 544 Pyridin-2-carboxylic acid {4-bromo-2-[N′-(4-methyl-benzyl)-hydrazinocarbonyl]-phenyl}-amide

The title compound 544 was produced in the same manner as in Example 7.

Mass spectrometric value (ESI-MS) 439 (M−1)

Compound 545 N-{2-[N′-(4-Methyl-benzyl)-hydrazinocarbonyl]-phenyl}-isonicotinamide

The title compound 545 was produced in the same manner as in Example 7.

Mass spectrometric value (ESI-MS) 359 (M−1)

Compound 546 N-{4-Bromo-2-[N′-(4-chloro-3-trifluoromethyl-benzyl)-hydrazinocarbonyl]-phenyl}-3-(2-hydroxy-ethylsulfanylmethyl)-benzamide

The title compound 546 was produced in the same manner as in Example 7.

Mass spectrometric value (ESI-MS) 614, 616, 617 (M−1)

Compound 547 N-{4-Chloro-2-[N′-(4-methyl-benzyl)-hydrazinocarbonyl]-phenyl}-3-(2-hydroxy-ethylsulfanylmethyl)-benzamide

The title compound 547 was produced in the same manner as in Example 7.

Mass spectrometric value (ESI-MS) 483 (M−1)

Compound 548 N-{4-Bromo-2-[N′-(3,4-dimethyl-benzyl)-hydrazinocarbonyl]-phenyl}-3,4-dimethoxy-benzamide

The title compound 548 was produced in the same manner as in Example 7.

Mass spectrometric value (ESI-MS) 508, 510 (M−1)

Compound 549 3-{[Bis-(2-hydroxy-ethyl)-amino]-methyl}-N-[4-chloro-2-(3-fluoro-benzylidene-hydrazinocarbonyl)-phenyl]-benzamide

The title compound 549 was produced in the same manner as in Example 5.

¹H-NMR (CD₃OD, 400 MHz): δ 8.66 (1H, d, J=9.0 Hz), 8.35 (1H, s), 8.07 (1H, s), 7.93-7.96 (1H, m), 7.85-7.96 (1H, m), 7.85-7.92 (1H, m), 7.71-7.76 (1H, m), 7.58-7.65 (3H, m), 7.40-7.54 (2H, m), 7.15-7.23 (1H, m), 3.83 (2H, s), 3.61-3.67 (4H, m), 2.67-2.74 (4H, m)

Mass spectrometric value (ESI-MS) 511, 513 (M−1)

Compound 550 3-{[Bis-(2-hydroxy-ethyl)-amino]-methyl}-N-[4-chloro-2-(4-fluoro-benzylidene-hydrazinocarbonyl)-phenyl]-benzamide

The title compound 550 was produced in the same manner as in Example 5.

¹H-NMR (CD₃OD, 400 MHz): δ 8.66 (1H, d, J=8.8 Hz), 8.35 (1H, s), 8.06 (1H, s), 7.87-7.95 (4H, m), 7.63 (1H, d, J=8.8 Hz), 7.62 (1H, d, J=8.8 Hz), 7.50 (1H, dd, J=7.6 Hz, J=7.6 Hz), 7.19 (2H, dd, J=8.8 Hz), 3.83 (2H, s), 3.65 (4H, t, J=5.9 Hz), 2.71 (4H, t, J=5.9 Hz)

Mass spectrometric value (ESI-MS) 511, 513 (M−1)

Example 8

Compound 551 N-[3-(3,4-Dimethyl-benzylidene-hydrazinocarbonyl)-4-methyl-thiophen-2-yl]-3-(1H-[1,2,4]triazol-3-ylsulfanylmethyl)-benzamide

Ethyl 2-amino-4-methylthiophene-3-carboxylate (compound A) (3.0 g) was dissolved in anhydrous methylene chloride (40.0 ml). Subsequently, pyridine (1.5 ml) and 3-(chloromethyl)benzoyl chloride (compound B) (2.8 ml) were added to the solution, and the mixture was stirred at 0° C. for one hr. After the completion of the reaction, distilled water was added, and the mixture was subjected to separatory extraction with chloroform. The organic layer was washed with saturated brine, was dried over sodium sulfate, and was then concentrated to give 2-(3-chloromethyl-benzoylamino-4-methyl-thiophene-3-carboxylic acid ethyl ester as a useful intermediate (3.80 g, yield 70%).

2-(3-Chloromethyl-benzoylamino-4-methyl-thiophene-3-carboxylic acid ethyl ester (700 mg) obtained by the above reaction was dissolved in anhydrous methylene chloride (5.0 ml), triethylamine (580 μl) and 3-mercapto-1,2,4-triazole (compound B′) (404 mg) were added to the solution at room temperature, and the mixture was stirred at room temperature for 15 hr. After the completion of the reaction, water was added at room temperature, and the reaction mixture was extracted by liquid separation using chloroform. The organic layer was washed with saturated brine, was dried over sodium sulfate, and was then concentrated. The residue was purified by column chromatography eluted with a chloroform-methanol system to give 4-methyl-2-[3(1H-[1,2,4]triazol-3-ylsulfanylmethyl)-benzoylamino]-thiophene-3-carboxylic acid ethyl ester as a useful intermediate (606 mg, yield 72%).

4-Methyl-2-[3(1H-[1,2,4]triazol-3-ylsulfanylmethyl)-benzoylamino]-thiophene-3-carboxylic acid ethyl ester produced by the above reaction was dissolved in ethanol (5.0 ml), hydrazine monohydrate (650 μl) was added to the solution, and the mixture was heated under reflux with stirring for 15 hr. After the completion of the reaction, water was added thereto at room temperature, and the mixture was subjected to separatory extraction with chloroform. The organic layer was washed with saturated brine, was dried over sodium sulfate, and was then concentrated to give a hydrazine compound N-(3-hydrazinocarbonyl-4-methyl-thiophen-2-yl)-3-(1H-[1,2,4]triazol-3-ylsulfanylmethyl)-benzamide (103 mg, crude yield 20%).

N-(3-Hydrazinocarbonyl-4-methyl-thiophen-2-yl)-3-(1H-[1,2,4]triazol-3-ylsulfanylmethyl)-benzamide (20 mg) was dissolved in anhydrous toluene (1.0 ml), 3,4-dimethylbenzaldehyde (compound C) (13.0 μl) was added to the solution at room temperature, and the mixture was heated under reflux with stirring for 15 hr. After the completion of the reaction, the reaction product was purified by column chromatography eluted with a chloroform-methanol system to give the title compound 551 (17.4 mg, yield 69%).

¹H-NMR (DMSO-d₆, 400 MHz): δ 2.25 (6H, s), 2.37 (3H, s), 4.40 (2H, s), 6.79 (1H, s), 7.15-8.00 (7H, m), 8.28 (1H, s), 8.56 (1H, s), 11.20-11.70 (2H, m), 14.05 (1H, s)

Mass spectrometric value (ESI-MS) 503 (M−1)

Compound 552 N-[4-Methyl-3-(4-methyl-benzylidene-hydrazinocarbonyl)-thiophen-2-yl]-3-(1H-[1,2,4]triazol-3-ylsulfanylmethyl)-benzamide

The title compound 552 was produced in substantially the same manner as in Example 8.

¹H-NMR (DMSO-d₆, 400 MHz): δ 2.34 (3H, s), 2.37 (3H, s), 4.40 (2H, s), 6.80 (1H, s), 7.20-8.00 (8H, m), 8.30 (1H, m), 8.57 (1H, s), 11.30-11.70 (2H, m), 14.10 (1H, s)

Mass spectrometric value (ESI-MS) 489 (M−1)

Compound 553 N-[3-(4-Fluoro-benzylidene-hydrazinocarbonyl)-4-methyl-thiophen-2-yl]-3-(1H-[1,2,4]-triazol-3-ylsulfanylmethyl)-benzamide

The title compound 553 was produced in substantially the same manner as in Example 8.

¹H-NMR (DMSO-d₆, 400 MHz): δ 2.36 (3H, s), 4.40 (2H, s), 6.81 (1H, s), 7.25-8.00 (8H, m), 8.40 (1H, m), 8.57 (1H, s), 11.30-11.70 (2H, m), 14.05 (1H, s)

Mass spectrometric value (ESI-MS) 493 (M−1)

Compound 554 N-[3-(3-Fluoro-benzylidene-hydrazinocarbonyl)-4-methyl-thiophen-2-yl]-3-(1H-[1,2,4]triazol-3-ylsulfanylmethyl)-benzamide

The title compound 554 was produced in substantially the same manner as in Example 8.

¹H-NMR (DMSO-d₆, 400 MHz): δ 2.35 (3H, s), 4.40 (2H, s), 6.81 (1H, s), 7.20-7.96 (8H, m), 8.36 (1H, s), 8.56 (1H, s), 11.40-11.75 (2H, m), 14.05 (1H, s)

Mass spectrometric value (ESI-MS) 493 (M−1)

Compound 555 N-[3-(4-Chloro-3-trifluoromethyl-benzylidene-hydrazinocarbonyl)-4-methyl-thiophen-2-yl]-3-(1H-[1,2,4]-triazol-3-ylsulfanylmethyl)-benzamide

The title compound 555 was produced in substantially the same manner as in Example 8.

¹H-NMR (DMSO-d₆, 400 MHz): δ 2.34 (3H, s), 4.38 (2H, s), 6.82 (1H, s), 7.40-8.58 (9H, m), 11.40-11.75 (2H, m), 14.05 (1H, s)

Mass spectrometric value (ESI-MS) 577 (M−1)

Compound 556 N-[3-(4-Methoxy-benzylidene-hydrazinocarbonyl)-4-methyl-thiophen-2-yl]-3-(1H-[1,2,4]triazol-3-ylsulfanylmethyl)-benzamide

The title compound 556 was produced in substantially the same manner as in Example 8.

¹H-NMR (DMSO-d₆, 400 MHz): δ 2.37 (3H, s), 3.80 (3H, s), 4.40 (2H, s), 6.80 (1H, s), 7.01 (2H, m), 7.40-7.74 (6H, m), 8.35 (1H, s), 8.57 (1H, s), 11.20-11.75 (2H, m), 14.05 (1H, s)

Mass spectrometric value (ESI-MS) 505 (M−1)

Compound 557 N-[3-(3,4-Dimethyl-benzylidene-hydrazinocarbonyl)-4-methyl-thiophen-2-yl]-3-(3-hydroxy-propylsulfanylmethyl)-benzamide

The title compound 557 was produced in substantially the same manner as in Example 8.

¹H-NMR (CD₃OD, 400 MHz): δ 1.77 (2H, m), 2.31 (6H, m), 2.50 (5H, m), 3.63 (2H, m), 3.82 (2H, s), 6.70 (1H, s), 7.19 (1H, d, J=7.8 Hz), 7.45-7.67 (4H, m), 7.80-7.95 (2H, m), 8.22 (1H, s)

Mass spectrometric value (ESI-MS) 494 (M−1)

Compound 558 3-(3-Hydroxy-propylsulfanylmethyl)-N-[4-methyl-3-(4-methyl-benzylidene-hydrazinocarbonyl)-thiophen-2-yl]-benzamide

The title compound 558 was produced in substantially the same manner as in Example 8.

¹H-NMR (CD₃OD, 400 MHz): δ 1.77 (2H, m), 2.38 (3H, s), 2.50 (5H, m), 3.60 (2H, t, J=6.4 Hz), 3.82 (2H, s), 6.71 (1H, d, J=0.96 Hz), 7.26 (2H, d, J=7.6 Hz), 7.50 (1H, m), 7.60 (1H, m), 7.73 (2H, m), 7.84 (1H, m), 7.92 (1H, s), 8.26 (1H, s)

Mass spectrometric value (ESI-MS) 480 (M−1)

Compound 559 N-[3-(4-Fluoro-benzylidene-hydrazinocarbonyl)-4-methyl-thiophen-2-yl]-3-(3-hydroxy-propylsulfanylmethyl)-benzamide

The title compound 559 was produced in substantially the same manner as in Example 8.

¹H-NMR (CD₃OD, 400 MHz): δ 1.77 (2H, m), 2.50 (5H, m), 3.62 (2H, m), 3.82 (2H, s), 6.71 (1H, s), 7.12 (2H, m), 7.50 (1H, m), 7.60 (1H, m), 7.87 (4H, m), 8.28 (1H, s)

Mass spectrometric value (ESI-MS) 484 (M−1)

Compound 560 N-[3-(3-Fluoro-benzylidene-hydrazinocarbonyl)-4-methyl-thiophen-2-yl]-3-(3-hydroxy-propylsulfanylmethyl)-benzamide

The title compound 560 was produced in substantially the same manner as in Example 8.

¹H-NMR (CD₃OD, 400 MHz): δ 1.77 (2H, m), 2.51 (5H, m), 3.60 (2H, t, J=6.2 Hz), 3.82 (2H, s), 6.72 (1H, s), 7.18 (1H, m), 7.42-7.65 (5H, m), 7.84 (1H, s), 7.93 (1H, s), 8.29 (1H, s)

Mass spectrometric value (ESI-MS) 484 (M−1)

Compound 561 N-[3-(4-Chloro-3-trifluoromethyl-benzylidene-hydrazinocarbonyl)-4-methyl-thiophen-2-yl]-3-(3-hydroxy-propylsulfanylmethyl)-benzamide

The title compound 561 was produced in substantially the same manner as in Example 8.

¹H-NMR (CD₃OD, 400 MHz): δ 1.77 (2H, m), 2.50 (5H, m), 3.60 (2H, t, J=6.1 Hz), 3.82 (2H, s), 6.72 (1H, s), 7.50 (1H, m), 7.61 (1H, d, J=7.3 Hz), 7.68 (1H, d, J=8.3 Hz), 7.84 (1H, m), 7.93 (1H, s), 8.05 (1H, m), 8.33 (2H, s)

Mass spectrometric value (ESI-MS) 568 (M−1)

Compound 562 3-(3-Hydroxy-propylsulfanylmethyl)-N-[3-(4-methoxy-benzylidene-hydrazinocarbonyl)-4-methyl-thiophen-2-yl]-benzamide

The title compound 562 was produced in substantially the same manner as in Example 8.

¹H-NMR (CD₃OD, 400 MHz): δ 1.77 (2H, m), 2.50 (5H, m), 3.60 (2H, t, J=6.2 Hz), 3.81 (2H, s), 3.84 (3H, s), 6.70 (1H, d, J=1.0 Hz), 6.99 (2H, d, J=8.3 Hz), 7.50 (1H, m), 7.60 (1H, m), 7.80 (3H, m), 7.92 (1H, s), 8.23 (1H, m)

Mass spectrometric value (ESI-MS) 496 (M−1)

Compound 563 3-{[(2-Diethylamino-ethyl)-methyl-amino]-methyl}-N-[3-(3,4-dimethyl-benzylidene-hydrazinocarbonyl)-4-methyl-thiophen-2-yl]-benzamide

The title compound 563 was produced in substantially the same manner as in Example 8.

¹H-NMR (CD₃OD, 400 MHz): δ 1.05 (6H, t, J=7.2 Hz), 2.26 (3H, s), 2.30 (3H, s), 2.31 (3H, s), 2.50 (2H, m), 2.57 (2H, m), 2.67 (5H, m), 2.79 (2H, m), 3.65 (2H, s), 6.64 (1H, s), 7.19 (1H, d, J=7.8 Hz), 7.46-7.65 (4H, m), 7.86-7.97 (2H, m), 8.21 (1H, s)

Mass spectrometric value (ESI-MS) 532 (M−1)

Compound 564 3-{[(2-Diethylamino-ethyl)-methyl-amino]-methyl}-N-[4-methyl-3-(4-methyl-benzylidene-hydrazinocarbonyl)-thiophen-2-yl]-benzamide

The title compound 564 was produced in substantially the same manner as in Example 8.

¹H-NMR (CD₃OD, 400 MHz): δ 1.05 (6H, t, J=7.3 Hz), 2.26 (3H, s), 2.38 (3H, s), 2.50 (2H, s), 2.57 (2H, m), 2.67 (5H, m), 2.78 (2H, m), 3.65 (2H, s), 6.63 (1H, s), 7.25 (2H, d, J=7.8 Hz), 7.51 (1H, dd, J=7.6 Hz, J=7.6 Hz), 7.58 (1H, d, J=7.6 Hz), 7.72 (2H, m), 7.91 (2H, m), 8.25 (1H, s)

Mass spectrometric value (ESI-MS) 518 (M−1)

Compound 565 3-{[(2-Diethylamino-ethyl)-methyl-amino]-methyl}-N-[3-(4-fluoro-benzylidene-hydrazinocarbonyl)-4-methyl-thiophen-2-yl]-benzamide

The title compound 565 was produced in substantially the same manner as in Example 8.

¹H-NMR (CD₃OD, 400 MHz): δ 1.05 (6H, m), 2.56 (3H, s), 2.49 (2H, m), 2.57 (2H, m), 2.66 (5H, m), 2.77 (2H, m), 3.64 (2H, s), 6.62 (1H, s), 7.16 (2H, dd, J=8.7 Hz, J=8.7 Hz), 7.50 (2H, m), 7.91 (4H, m), 8.27 (1H, s)

Mass spectrometric value (ESI-MS) 522 (M−1)

Compound 566 3-{[(2-Diethylamino-ethyl)-methyl-amino]-methyl}-N-[3-(3-fluoro-benzylidene-hydrazinocarbonyl)-4-methyl-thiophen-2-yl]-benzamide

The title compound 566 was produced in substantially the same manner as in Example 8.

¹H-NMR (CD₃OD, 400 MHz): δ 1.07 (6H, t, J=7.2 Hz), 2.26 (3H, m), 2.50 (2H, s), 2.58 (2H, m), 2.72 (5H, m), 2.83 (2H, m), 3.65 (2H, s), 6.62 (1H, s), 7.15 (1H, ddd, J=8.3 Hz, J=8.3 Hz, J=1.7 Hz), 7.40-7.80 (5H, m), 7.87-7.90 (2H, m), 8.27 (1H, s)

Mass spectrometric value (ESI-MS) 522 (M−1)

Compound 567 N-[3-(4-Chloro-3-trifluoromethyl-benzylidene-hydrazinocarbonyl)-4-methyl-thiophen-2-yl]-3-{[(2-diethylamino-ethyl)-methyl-amino]-methyl}-benzamide

The title compound 567 was produced in substantially the same manner as in Example 8.

¹H-NMR (CD₃OD, 400 MHz): δ 1.06 (6H, t, J=7.3 Hz), 2.26 (3H, m), 2.49 (2H, s), 2.57 (2H, m), 2.68 (5H, m), 2.80 (2H, m), 3.64 (2H, s), 6.60 (1H, s), 7.50 (1H, m), 7.57 (1H, d, J=7.6 Hz), 7.65 (1H, d, J=8.3 Hz), 7.94 (3H, m), 8.28 (2H, m)

Mass spectrometric value (ESI-MS) 606 (M−1)

Compound 568 3-{[(2-Diethylamino-ethyl)-methyl-amino]-methyl}-N-[3-(4-methoxy-benzylidene-hydrazinocarbonyl)-4-methyl-thiophen-2-yl]-benzamide

The title compound 568 was produced in substantially the same manner as in Example 8.

¹H-NMR (CD₃OD, 400 MHz): δ 1.05 (6H, t, J=7.2 Hz), 2.25 (3H, s), 2.49 (2H, s), 2.57 (2H, m), 2.66 (5H, m), 2.77 (2H, m), 3.64 (2H, m), 3.83 (3H, s), 6.63 (1H, s), 6.97 (2H, d, J=8.5 Hz), 7.42-7.59 (2H, m), 7.76 (2H, m), 7.90 (2H, m), 8.22 (1H, s)

Mass spectrometric value (ESI-MS) 534 (M−1)

Compound 569 3-[1,4′]Bipiperidinyl-1′-ylmethyl-N-[3-(3,4-dimethyl-benzylidene-hydrazinocarbonyl)-4-methyl-thiophen-2-yl]-benzamide

The title compound 569 was produced in substantially the same manner as in Example 8.

¹H-NMR (CD₃OD, 400 MHz): δ 1.49 (2H, m), 1.64 (6H, m), 1.87 (2H, m), 2.03 (2H, m), 2.27 (1H, m), 2.29 (6H, m), 2.49 (3H, s), 2.71 (4H, m), 2.96 (2H, d, J=11.0 Hz), 3.59 (2H, s), 6.66 (1H, s), 7.18 (1H, d, J=7.6 Hz), 7.45-7.73 (4H, m), 7.88 (2H, s), 8.22 (1H, s)

Mass spectrometric value (ESI-MS) 570 (M−1)

Compound 570 3-[1,4′]Bipiperidinyl-1′-ylmethyl-N-[4-methyl-3-(4-methyl-benzylidene-hydrazinocarbonyl)-thiophen-2-yl]-benzamide

The title compound 570 was produced in substantially the same manner as in Example 8.

¹H-NMR (CD₃OD, 400 MHz): δ 1.49 (2H, m), 1.65 (6H, m), 1.88 (2H, d, J=11.0 Hz), 2.04 (2H, t, J=11.5 Hz), 2.34 (1H, s), 2.37 (3H, s), 2.49 (3H, s), 2.74 (4H, bs), 2.97 (2H, d, J=11.2 Hz), 3.58 (2H, s), 6.67 (1H, s), 7.24 (2H, d, J=7.8 Hz), 7.45-7.60 (2H, m), 7.70 (2H, m), 7.85-7.95 (2H, m), 8.26 (1H, s)

Mass spectrometric value (ESI-MS) 556 (M−1)

Compound 571 3-[1,4′]Bipiperidinyl-1′-ylmethyl-N-[3-(4-fluoro-benzylidene-hydrazinocarbonyl)-4-methyl-thiophen-2-yl]-benzamide

The title compound 571 was produced in substantially the same manner as in Example 8.

¹H-NMR (CD₃OD, 400 MHz): δ 1.48 (2H, m), 1.63 (6H, m), 1.86 (2H, d, J=11.4 Hz), 2.03 (2H, t, J=11.2 Hz), 2.36-2.54 (4H, m), 2.66 (4H, m), 2.96 (2H, d, J=11.2 Hz), 3.58 (2H, s), 6.66 (1H, s), 7.17 (2H, dd, J=8.5 Hz, J=8.5 Hz), 7.45-7.60 (2H, m), 7.85-7.94 (4H, m), 8.28 (1H, s)

Mass spectrometric value (ESI-MS) 560 (M−1)

Compound 572 3-[1,4′]Bipiperidinyl-1′-ylmethyl-N-[3-(3-fluoro-benzylidene-hydrazinocarbonyl)-4-methyl-thiophen-2-yl]-benzamide

The title compound 572 was produced in substantially the same manner as in Example 8.

¹H-NMR (CD₃OD, 400 MHz): δ 1.49 (2H, m), 1.64 (6H, m), 1.87 (2H, d, J=11.7 Hz), 2.03 (2H, t, J=11.2 Hz), 2.49 (4H, s), 2.72 (4H, m), 2.96 (2H, d, J=11.5 Hz), 3.58 (2H, s), 6.65 (1H, s), 7.15 (1H, m), 7.40-7.75 (5H, m), 7.85-7.95 (2H, m), 8.28 (1H, s)

Mass spectrometric value (ESI-MS) 560 (M−1)

Compound 573 3-[1,4′]Bipiperidinyl-1′-ylmethyl-N-[3-(4-chloro-3-trifluoromethyl-benzylidene-hydrazinocarbonyl)-4-methyl-thiophen-2-yl]-benzamide

The title compound 573 was produced in substantially the same manner as in Example 8.

¹H-NMR (CD₃OD, 400 MHz): δ 1.49 (2H, m), 1.63 (6H, m), 1.87 (2H, d, J=11.2 Hz), 2.04 (2H, t, J=11.1 Hz), 2.40-2.54 (4H, m), 2.68 (4H, m), 2.97 (2H, d, J=11.5 Hz), 3.59 (2H, s), 6.65 (1H, s), 7.45-7.60 (2H, m), 7.67 (1H, d, J=8.3 Hz), 7.85-8.05 (3H, m), 8.31 (2H, m)

Mass spectrometric value (ESI-MS) 644 (M−1)

Compound 574 3-[1,4′]Bipiperidinyl-1′-ylmethyl-N-[3-(4-methoxy-benzylidene-hydrazinocarbonyl)-4-methyl-thiophen-2-yl]-benzamide

The title compound 574 was produced in substantially the same manner as in Example 8.

¹H-NMR (CD₃OD, 400 MHz): δ 1.49 (2H, m), 1.61 (6H, m), 1.85 (2H, d, J=11.7 Hz), 2.02 (2H, t, J=11.6 Hz), 2.30-2.52 (4H, m), 2.65 (4H, bs), 2.95 (2H, d, J=11.0 Hz), 3.58 (2H, s), 3.83 (3H, s), 6.66 (1H, s), 6.98 (2H, d, J=8.3 Hz), 7.44-7.61 (2H, m), 7.76 (2H, m), 7.90 (2H, m), 8.23 (1H, s)

Mass spectrometric value (ESI-MS) 572 (M−1)

Compound 575 N-[3-(3,4-Dimethyl-benzylidene-hydrazinocarbonyl)-4-methyl-thiophen-2-yl]-3-[4-(2-hydroxy-ethyl)-piperazin-1-ylmethyl]-benzamide

The title compound 575 was produced in substantially the same manner as in Example 8.

¹H-NMR (CD₃OD, 400 MHz): δ 2.29 (6H, s), 2.48 (3H, s), 2.52-2.70 (10H, m), 3.62 (2H, s), 3.66 (2H, t, J=6.0 Hz), 6.68 (1H, d, J=1.0 Hz), 7.17 (1H, d, J=7.6 Hz), 7.50 (2H, m), 7.59 (2H, m), 7.80-7.95 (2H, m), 8.22 (1H, s)

Mass spectrometric value (ESI-MS) 532 (M−1)

Compound 576 3-[4-(2-Hydroxy-ethyl)-piperazin-1-ylmethyl]-N-[4-methyl-3-(4-methyl-benzylidene-hydrazinocarbonyl)-thiophen-2-yl]-benzamide

The title compound 576 was produced in substantially the same manner as in Example 8.

¹H-NMR (CD₃OD, 400 MHz): δ 2.38 (3H, s), 2.49 (3H, s), 2.54-2.74 (10H, m), 3.60-3.70 (4H, m), 6.71 (1H, d, J=1.2 Hz), 7.25 (2H, d, J=7.6 Hz), 7.51 (1H, dd, J=7.4 Hz, J=7.4 Hz), 7.59 (1H, d, J=7.4 Hz), 7.71 (2H, bs), 7.85-7.95 (2H, m), 8.26 (1H, s)

Mass spectrometric value (ESI-MS) 518 (M−1)

Compound 577 N-[3-(4-Fluoro-benzylidene-hydrazinocarbonyl)-4-methyl-thiophen-2-yl]-3-[4-(2-hydroxy-ethyl)-piperazin-1-ylmethyl]-benzamide

The title compound 577 was produced in substantially the same manner as in Example 8.

¹H-NMR (CD₃OD, 400 MHz): δ 2.49 (3H, m), 2.52-2.76 (10H, m), 3.63 (2H, s), 3.68 (2H, t, J=5.8 Hz), 6.69 (1H, d, J=1.0 Hz), 7.17 (2H, dd, J=8.6 Hz, J=8.6 Hz), 7.50 (1H, dd, J=7.6 Hz, J=7.6 Hz), 7.59 (1H, d, J=7.6 Hz), 7.82-7.94 (4H, m), 8.28 (1H, s)

Mass spectrometric value (ESI-MS) 522 (M−1)

Compound 578 N-[3-(3-Fluoro-benzylidene-hydrazinocarbonyl)-4-methyl-thiophen-2-yl]-3-[4-(2-hydroxy-ethyl)-piperazin-1-ylmethyl]-benzamide

The title compound 578 was produced in substantially the same manner as in Example 8.

¹H-NMR (CD₃OD, 400 MHz): δ 2.49 (3H, s), 2.57 (4H, m), 2.64 (2H, t, J=5.9 Hz), 2.71 (4H, m), 3.63 (2H, s), 3.68 (2H, t, J=5.9 Hz), 6.68 (1H, d, J=1.0 Hz), 7.16 (1H, dd, J=8.1 Hz, J=8.1 Hz), 7.40-7.70 (5H, m), 7.82-7.95 (2H, m), 8.28 (1H, s)

Mass spectrometric value (ESI-MS) 522 (M−1)

Compound 579 N-[3-(4-Chloro-3-trifluoromethyl-benzylidene-hydrazinocarbonyl)-4-methyl-thiophen-2-yl]-3-[4-(2-hydroxy-ethyl)-piperazin-1-ylmethyl]-benzamide

The title compound 579 was produced in substantially the same manner as in Example 8.

¹H-NMR (CD₃OD, 400 MHz): δ 2.49 (3H, s), 2.52-2.68 (10H, m), 3.63 (2H, s), 3.66 (2H, t, J=6.0 Hz), 6.70 (1H, d, J=1.0 Hz), 7.51 (1H, dd, J=7.3 Hz, J=7.3 Hz), 7.60 (1H, d, J=7.3 Hz), 7.67 (1H, d, J=8.3 Hz), 7.87 (1H, m), 7.93 (1H, s), 8.00 (1H, bs), 8.32 (2H, m)

Mass spectrometric value (ESI-MS) 606 (M−1)

Compound 580 3-[4-(2-Hydroxy-ethyl)-piperazin-1-ylmethyl]-N-[3-(4-methoxy-benzylidene-hydrazinocarbonyl)-4-methyl-thiophen-2-yl]-benzamide

The title compound 580 was produced in substantially the same manner as in Example 8.

¹H-NMR (CD₃OD, 400 MHz): δ 2.49 (3H, s), 2.50-2.75 (10H, m), 3.63 (2H, s), 3.67 (2H, t, J=6.0 Hz), 3.83 (3H, s), 6.69 (1H, d, J=1.0 Hz), 6.98 (2H, d, J=8.3 Hz), 7.50 (1H, dd, J=7.6 Hz, J=7.6 Hz), 7.59 (1H, d, J=7.6 Hz), 7.76 (2H, m), 7.82-7.94 (2H, m), 8.23 (1H, s)

Mass spectrometric value (ESI-MS) 534 (M−1)

Compound 581 3-[(2-Diethylamino-ethylamino)-methyl]-N-[3-(3,4-dimethyl-benzylidene-hydrazinocarbonyl)-4-methyl-thiophen-2-yl]-benzamide

The title compound 581 was produced in substantially the same manner as in Example 8.

¹H-NMR (CD₃OD, 400 MHz): δ 1.20 (6H, t, J=7.2 Hz), 2.31 (3H, s), 2.32 (3H, s), 2.51 (3H, s), 2.91 (2H, t, J=6.2 Hz), 3.02 (6H, m), 3.97 (2H, s), 6.71 (1H, d, J=1.0 Hz), 7.20 (1H, d, J=7.8 Hz), 7.50-7.70 (4H, m), 7.91 (1H, m), 7.99 (1H, m), 8.25 (1H, s)

Mass spectrometric value (ESI-MS) 518 (M−1)

Compound 582 3-[(2-Diethylamino-ethylamino)-methyl]-N-[4-methyl-3-(4-methyl-benzylidene-hydrazinocarbonyl)-thiophen-2-yl]-benzamide

The title compound 582 was produced in substantially the same manner as in Example 8.

¹H-NMR (CD₃OD, 400 MHz): δ 1.22 (6H, t, J=7.2 Hz), 2.39 (3H, s), 2.51 (3H, s), 2.93 (2H, t, J=6.2 Hz), 3.06 (6H, m), 3.39 (2H, s), 6.72 (1H, d, J=1.0 Hz), 7.27 (2H, d, J=7.8 Hz), 7.52-7.77 (4H, m), 7.91 (1H, m), 8.01 (1H, m), 8.28 (1H, s)

Mass spectrometric value (ESI-MS) 504 (M−1)

Compound 583 3-[(2-Diethylamino-ethylamino)-methyl]-N-[3-(4-fluoro-benzylidene-hydrazinocarbonyl)-4-methyl-thiophen-2-yl]-benzamide

The title compound 583 was produced in substantially the same manner as in Example 8.

¹H-NMR (CD₃OD, 400 MHz): δ 1.19 (6H, t, J=7.2 Hz), 2.52 (3H, s), 2.89 (2H, t, J=6.1 Hz), 2.98 (6H, m), 3.96 (2H, s), 6.72 (1H, d, J=1.0 Hz), 7.19 (2H, dd, J=8.7 Hz, J=8.7 Hz), 7.56 (1H, m), 7.64 (1H, d, J=7.2 Hz), 7.90 (3H, m), 7.99 (1H, s), 8.30 (1H, s)

Mass spectrometric value (ESI-MS) 509 (M−1)

Compound 584 3-[(2-Diethylamino-ethylamino)-methyl]-N-[3-(3-fluoro-benzylidene-hydrazinocarbonyl)-4-methyl-thiophen-2-yl]-benzamide

The title compound 584 was produced in substantially the same manner as in Example 8.

¹H-NMR (CD₃OD, 400 MHz): δ 1.20 (6H, t, J=7.2 Hz), 2.52 (3H, s), 2.90 (2H, m), 3.00 (6H, m), 3.96 (2H, s), 6.71 (1H, d, J=1.2 Hz), 7.18 (1H, dd, J=8.3 Hz, J=8.3 Hz), 7.46 (1H, m), 7.52-7.75 (4H, m), 7.91 (1H, m), 7.99 (1H, s), 8.31 (1H, s)

Mass spectrometric value (ESI-MS) 508 (M−1)

Compound 585 N-[3-(4-Chloro-3-trifluoromethyl-benzylidene-hydrazinocarbonyl)-4-methyl-thiophen-2-yl]-3-[(2-diethylamino-ethylamino)-methyl]-benzamide

The title compound 585 was produced in substantially the same manner as in Example 8.

¹H-NMR (CD₃OD, 400 MHz): δ 1.16 (6H, t, J=7.2 Hz), 2.51 (3H, s), 2.91 (8H, m), 3.95 (2H, s), 6.70 (1H, d, J=1.2 Hz), 7.55 (1H, m), 7.64 (1H, d, J=8.0 Hz), 7.69 (1H, d, J=8.3 Hz), 7.91 (1H, m), 7.98 (2H, m), 8.34 (2H, s)

Mass spectrometric value (ESI-MS) 592 (M−1)

Compound 586 3-[(2-Diethylamino-ethylamino)-methyl]-N-[3-(4-methoxy-benzylidene-hydrazinocarbonyl)-4-methyl-thiophen-2-yl]-benzamide

The title compound 586 was produced in substantially the same manner as in Example 8.

¹H-NMR (CD₃OD, 400 MHz): δ 1.16 (6H, t, J=7.2 Hz), 2.51 (3H, s), 2.90 (8H, m), 3.85 (3H, s), 3.94 (2H, s), 6.70 (1H, d, J=1.0 Hz), 6.99 (2H, d, J=8.8 Hz), 7.56 (1H, m), 7.64 (1H, m), 7.79 (2H, d, J=7.3 Hz), 7.91 (1H, m), 7.98 (1H, s), 8.25 (1H, s)

Mass spectrometric value (ESI-MS) 520 (M−1)

Compound 587 3-{[Bis-(2-hydroxy-propyl)-amino]-methyl}-N-[3-(3,4-dimethyl-benzylidene-hydrazinocarbonyl)-4-methyl-thiophen-2-yl]-benzamide

The title compound 587 was produced in substantially the same manner as in Example 8.

¹H-NMR (CD₃OD, 400 MHz): δ 1.09 (6H, m), 2.31 (6H, m), 2.51 (7H, m), 3.60-3.95 (4H, m), 6.70 (1H, d, J=1.0 Hz), 7.19 (1H, d, J=8.0 Hz), 7.52 (2H, m), 7.65 (2H, d, J=6.6 Hz), 7.87 (1H, m), 7.99 (1H, s), 8.22 (1H, s)

Mass spectrometric value (ESI-MS) 535 (M−1)

Compound 588 3-{[Bis-(2-hydroxy-propyl)-amino]-methyl}-N-[4-methyl-3-(4-methyl-benzylidene-hydrazinocarbonyl)-thiophen-2-yl]-benzamide

The title compound 588 was produced in substantially the same manner as in Example 8.

¹H-NMR (CD₃OD, 400 MHz): δ 1.09 (6H, m), 2.38 (3H, s), 2.51 (7H, m), 3.68-3.94 (4H, m), 6.70 (1H, d, J=1.2 Hz), 7.25 (2H, m), 7.51 (1H, m), 7.65 (1H, d, J=7.3 Hz), 7.73 (2H, m), 7.87 (1H, m), 7.99 (1H, s), 8.26 (1H, s)

Mass spectrometric value (ESI-MS) 521 (M−1)

Compound 589 3-{[Bis-(2-hydroxy-propyl)-amino]-methyl}-N-[3-(4-fluoro-benzylidene-hydrazinocarbonyl)-4-methyl-thiophen-2-yl]-benzamide

The title compound 589 was produced in substantially the same manner as in Example 8.

¹H-NMR (CD₃OD, 400 MHz): δ 1.09 (6H, m), 2.49 (7H, m), 3.65-3.95 (4H, m), 6.71 (1H, m), 7.18 (2H, dd, J=8.8 Hz, J=8.8 Hz), 7.51 (1H, dd, J=7.4 Hz, J=7.4 Hz), 7.65 (1H, d, J=7.4 Hz), 7.88 (3H, m), 7.99 (1H, s), 8.29 (1H, s)

Mass spectrometric value (ESI-MS) 526 (M−1)

Compound 590 3-{[Bis-(2-hydroxy-propyl)-amino]-methyl}-N-[3-(3-fluoro-benzylidene-hydrazinocarbonyl)-4-methyl-thiophen-2-yl]-benzamide

The title compound 590 was produced in substantially the same manner as in Example 8.

¹H-NMR (CD₃OD, 400 MHz): δ 1.09 (6H, m), 2.49 (7H, m), 3.87 (4H, m), 6.71 (1H, d, J=1.0 Hz), 7.17 (2H, m), 7.40-7.75 (4H, m), 7.87 (1H, d, J=7.8 Hz), 8.00 (1H, s), 8.29 (1H, s)

Mass spectrometric value (ESI-MS) 525 (M−1)

Compound 591 3-{[Bis-(2-hydroxy-propyl)-amino]-methyl}-N-[3-(4-chloro-3-trifluoromethyl-benzylidene-hydrazinocarbonyl)-4-methyl-thiophen-2-yl]-benzamide

The title compound 591 was produced in substantially the same manner as in Example 8.

¹H-NMR (CD₃OD, 400 MHz): δ 1.08 (6H, m), 2.50 (7H, m), 3.65-3.95 (4H, m), 6.71 (1H, d, J=1.0 Hz), 7.51 (1H, dd, J=7.6 Hz, J=7.6 Hz), 7.66 (2H, m), 7.86 (1H, m), 8.02 (2H, m), 8.33 (2H, m)

Mass spectrometric value (ESI-MS) 609 (M−1)

Compound 592 3-{[Bis-(2-hydroxy-propyl)-amino]-methyl}-N-[3-(4-methoxy-benzylidene-hydrazinocarbonyl)-4-methyl-thiophen-2-yl]-benzamide

The title compound 592 was produced in substantially the same manner as in Example 8.

¹H-NMR (CD₃OD, 400 MHz): δ 1.09 (6H, d, J=6.1 Hz), 2.49 (7H, m), 3.85 (7H, m), 6.70 (1H, d, J=1.0 Hz), 6.99 (2H, d, J=8.3 Hz), 7.51 (1H, m), 7.65 (1H, d, J=7.6 Hz), 7.84 (3H, m), 7.99 (1H, s), 8.23 (1H, s)

Mass spectrometric value (ESI-MS) 537 (M−1)

Compound 593 N-[3-(3,4-Dimethyl-benzylidene-hydrazinocarbonyl)-4-methyl-thiophen-2-yl]-3-(4-hydroxy-piperidin-1-ylmethyl]-benzamide

The title compound 593 was produced in substantially the same manner as in Example 8.

¹H-NMR (CD₃OD, 400 MHz): δ 1.59 (2H, m), 1.85 (2H, m), 2.29 (8H, bs), 2.48 (3H, s), 2.84 (2H, m), 3.66 (3H, m), 6.68 (1H, d, J=1.0 Hz), 7.17 (1H, d, J=7.6 Hz), 7.52 (1H, m), 7.61 (2H, d, J=5.6 Hz), 7.89 (2H, m), 8.22 (1H, s)

Mass spectrometric value (ESI-MS) 503 (M−1)

Compound 594 3-(4-Hydroxy-piperidin-1-ylmethyl)-N-[4-methyl-3-(4-methyl-benzylidene-hydrazinocarbonyl)-thiophen-2-yl]-benzamide

The title compound 594 was produced in substantially the same manner as in Example 8.

¹H-NMR (CD₃OD, 400 MHz): δ 1.59 (2H, m), 1.86 (2H, m), 2.35 (5H, m), 2.49 (3H, s), 2.87 (2H, m), 3.67 (3H, m), 6.70 (1H, d, J=1.2 Hz), 7.25 (2H, d, J=7.8 Hz), 7.53 (1H, dd, J=7.3 Hz, J=7.3 Hz), 7.63 (1H, d, J=7.3 Hz), 7.71 (2H, m), 7.91 (2H, m), 8.26 (1H, s)

Mass spectrometric value (ESI-MS) 489 (M−1)

Compound 595 N-[3-(4-Fluoro-benzylidene-hydrazinocarbonyl)-4-methyl-thiophen-2-yl]-3-(4-hydroxy-piperidin-1-ylmethyl)-benzamide

The title compound 595 was produced in substantially the same manner as in Example 8.

¹H-NMR (CD₃OD, 400 MHz): δ 1.62 (2H, m), 1.87 (2H, m), 2.36 (2H, m), 2.49 (3H, s), 2.89 (21-1, m), 3.66 (1H, m), 3.74 (2H, s), 6.72 (1H, d, J=1.0 Hz), 7.18 (2H, dd, J=8.6 Hz, J=8.6 Hz), 7.54 (1H, m), 7.64 (1H, d, J=7.3 Hz), 7.91 (4H, m), 8.29 (1H, s)

Mass spectrometric value (ESI-MS) 493 (M−1)

Compound 596 N-[3-(3-Fluoro-benzylidene-hydrazinocarbonyl)-4-methyl-thiophen-2-yl]-3-(4-hydroxy-piperidin-1-ylmethyl)-benzamide

The title compound 596 was produced in substantially the same manner as in Example 8.

¹H-NMR (CD₃OD, 400 MHz): δ 1.60 (2H, m), 1.87 (2H, m), 2.35 (2H, m), 2.49 (3H, s), 2.88 (2H, m), 3.66 (1H, m), 3.72 (2H, s), 6.69 (1H, d, J=1.1 Hz), 7.16 (1H, dd, J=8.3 Hz, J=8.3 Hz), 7.44 (1H, m), 7.53 (2H, m), 7.63 (2H, m), 7.91 (2H, m), 8.28 (1H, s)

Mass spectrometric value (ESI-MS) 493 (M−1)

Compound 597 N-[3-(4-Chloro-3-trifluoromethyl-benzylidene-hydrazinocarbonyl)-4-methyl-thiophen-2-yl]-3-(4-hydroxy-piperidin-1-ylmethyl)-benzamide

The title compound 597 was produced in substantially the same manner as in Example 8.

¹H-NMR (CD₃OD, 400 MHz): δ 1.61 (2H, m), 1.86 (2H, m), 2.37 (2H, m), 2.50 (3H, s), 2.90 (2H, m), 3.67 (1H, m), 3.74 (2H, s), 6.72 (1H, d, J=1.0 Hz), 7.55 (1H, dd, J=7.5 Hz, J=7.5 Hz), 7.66 (2H, m), 7.92 (3H, m), 8.33 (2H, m)

Mass spectrometric value (ESI-MS) 577 (M−1)

Compound 598 3-(4-Hydroxy-piperidin-1-ylmethyl)-N-[3-(4-methoxy-benzylidene-hydrazinocarbonyl)-4-methyl-thiophen-2-yl]-benzamide

The title compound 598 was produced in substantially the same manner as in Example 8.

¹H-NMR (CD₃OD, 400 MHz): δ 1.61 (2H, m), 1.87 (2H, m), 2.37 (2H, m), 2.49 (3H, s), 2.89 (2H, m), 3.66 (1H, m), 3.73 (2H, s), 3.84 (3H, s), 6.69 (1H, d, J=1.0 Hz), 6.97 (2H, d, J=8.3 Hz), 7.53 (1H, m), 7.62 (1H, m), 7.76 (2H, m), 7.90 (2H, m), 8.23 (1H, s)

Mass spectrometric value (ESI-MS) 505 (M−1)

Compound 599 N-[3-(3,4-Dimethyl-benzylidene-hydrazinocarbonyl)-4-methyl-thiophen-2-yl]-3-(4-hydroxymethyl-piperidin-1-ylmethyl)-benzamide

The title compound 599 was produced in substantially the same manner as in Example 8.

¹H-NMR (CD₃OD, 400 MHz): δ 1.29 (2H, m), 1.50 (1H, m), 1.75 (2H, d, J=11.5 Hz), 2.19 (2H, m), 2.30 (6H, s), 2.49 (3H, s), 2.99 (2H, d, J=10.8 Hz), 3.38 (2H, d, J=6.6 Hz), 3.73 (2H, s), 6.70 (1H, d, J=1.0 Hz), 7.19 (1H, d, J=7.6 Hz), 7.54 (2H, m), 7.62 (2H, m), 7.91 (2H, m), 8.22 (1H, s)

Mass spectrometric value (ESI-MS) 517 (M−1)

Compound 600 3-(4-Hydroxymethyl-piperidin-1-ylmethyl)-N-[4-methyl-3-(4-methyl-benzylidene-hydrazinocarbonyl)-thiophen-2-yl]-benzamide

The title compound 600 was produced in substantially the same manner as in Example 8.

¹H-NMR (CD₃OD, 400 MHz): δ 1.30 (2H, m), 1.50 (1H, m), 1.75 (2H, d, J=13.2 Hz), 2.22 (2H, t, J=11.5 Hz), 2.37 (3H, s), 2.48 (3H, s), 3.00 (2H, d, J=11.0 Hz), 3.38 (2H, d, J=6.3 Hz), 3.74 (2H, s), 6.68 (1H, d, J=1.0 Hz), 7.24 (2H, d, J=7.8 Hz), 7.52 (1H, dd, J=7.4 Hz, J=7.4 Hz), 7.62 (1H, d, J=7.4 Hz), 7.69 (2H, m), 7.90 (2H, m), 8.25 (1H, s)

Mass spectrometric value (ESI-MS) 503 (M−1)

Compound 601 N-[3-(4-Fluoro-benzylidene-hydrazinocarbonyl)-4-methyl-thiophen-2-yl]-3-(4-hydroxymethyl-piperidin-1-ylmethyl)-benzamide

The title compound 601 was produced in substantially the same manner as in Example 8.

¹H-NMR (CD₃OD, 400 MHz): δ 1.30 (2H, m), 1.50 (1H, m), 1.75 (2H, d, J=12.2 Hz), 2.22 (2H, t, J=11.4 Hz), 2.48 (3H, s), 3.01 (2H, d, J=11.2 Hz), 3.38 (2H, d, J=6.4 Hz), 3.73 (2H, s), 6.68 (1H, d, J=1.0 Hz), 7.16 (2H, dd, J=8.6 Hz, J=8.6 Hz), 7.52 (1H, dd, J=7.6 Hz, J=7.6 Hz), 7.62 (1H, d, J=7.6 Hz), 7.88 (4H, m), 8.28 (1H, s)

Mass spectrometric value (ESI-MS) 507 (M−1)

Compound 602 N-[3-(3-Fluoro-benzylidene-hydrazinocarbonyl)-4-methyl-thiophen-2-yl]-3-(4-hydroxymethyl-piperidin-1-ylmethyl)-benzamide

The title compound 602 was produced in substantially the same manner as in Example 8.

¹H-NMR (CD₃OD, 400 MHz): δ 1.31 (2H, m), 1.51 (1H, m), 1.76 (2H, d, J=11.5 Hz), 2.23 (2H, d, J=10.8 Hz), 2.45 (3H, s), 3.02 (2H, d, J=11.2 Hz), 3.39 (2H, d, J=6.3 Hz), 3.75 (2H, s), 6.69 (1H, d, J=1.0 Hz), 7.17 (1H, m), 7.44 (1H, m), 7.53 (2H, m), 7.63 (2H, m), 7.90 (2H, m), 8.28 (1H, s)

Mass spectrometric value (ESI-MS) 507 (M−1)

Compound 603 N-[3-(4-Chloro-3-trifluoromethyl-benzylidene-hydrazinocarbonyl)-4-methyl-thiophen-2-yl]-3-(4-hydroxymethyl-piperidin-1-ylmethyl)-benzamide

The title compound 603 was produced in substantially the same manner as in Example 8.

¹H-NMR (CD₃OD, 400 MHz): δ 1.31 (2H, m), 1.51 (1H, m), 1.76 (2H, d, J=11.7 Hz), 2.21 (2H, t, J=11.5 Hz), 2.49 (3H, s), 3.01 (2H, d, J=11.5 Hz), 3.38 (2H, d, J=6.3 Hz), 3.74 (2H, s), 6.70 (1H, s), 7.54 (1H, dd, J=7.4 Hz), 7.65 (2H, m), 7.94 (3H, m), 8.31 (2H, m)

Mass spectrometric value (ESI-MS) 591 (M−1)

Compound 604 3-(4-Hydroxymethyl-piperidin-1-ylmethyl)-N-[3-(4-methoxy-benzylidene-hydrazinocarbonyl)-4-methyl-thiophen-2-yl]-benzamide

The title compound 604 was produced in substantially the same manner as in Example 8.

¹H-NMR (CD₃OD, 400 MHz): δ 1.29 (2H, m), 1.50 (1H, m), 1.75 (2H, d, J=12.2 Hz), 2.20 (2H, t, J=11.1 Hz), 2.47 (3H, s), 3.00 (2H, d, J=10.8 Hz), 3.38 (2H, d, J=6.4 Hz), 3.72 (2H, s), 3.83 (3H, s), 6.67 (1H, s), 6.96 (2H, d, J=8.3 Hz), 7.51 (1H, dd, J=7.4 Hz), 7.61 (1H, d, J=7.4 Hz), 7.75 (2H, d, J=6.4 Hz), 7.89 (2H, m), 8.23 (1H, m)

Mass spectrometric value (ESI-MS) 519 (M−1)

Compound 605 N-[3-(3,4-Dimethyl-benzylidene-hydrazinocarbonyl)-4,5,6,7-tetrahydro-benzo[b]thiophen-2-yl]-3-(3-hydroxy-propylsulfanyl-methyl)-benzamide

The title compound 605 was produced in substantially the same manner as in Example 8.

¹H-NMR (CD₃OD, 400 MHz): δ 1.77 (2H, m), 1.89 (4H, m), 2.30 (6H, s), 2.51 (2H, t, J=7.2 Hz), 2.74 (2H, m), 2.85 (2H, m), 3.60 (2H, t, J=6.2 Hz), 3.82 (2H, s), 7.19 (1H, d, J=7.6 Hz), 7.51 (2H, m), 7.61 (2H, m), 7.87 (2H, m), 8.21 (1H, s)

Mass spectrometric value (ESI-MS) 534 (M−1)

Compound 606 N-[3-(4-Fluoro-benzylidene-hydrazinocarbonyl)-4,5,6,7-tetrahydro-benzo[b]thiophen-2-yl]-3-(3-hydroxy-propylsulfanylmethyl)-benzamide

The title compound 606 was produced in substantially the same manner as in Example 8.

¹H-NMR (CD₃OD, 400 MHz): δ 1.77 (2H, m), 1.89 (4H, m), 2.51 (2H, t, J=7.3 Hz), 2.75 (2H, m), 2.86 (2H, m), 3.60 (2H, t, J=6.2 Hz), 3.82 (2H, s), 7.18 (2H, dd, J=8.8 Hz, J=8.8 Hz), 7.50 (1H, dd, J=7.6 Hz, J=7.6 Hz), 7.60 (1H, d, J=7.6 Hz), 7.87 (2H, m), 8.06 (2H, m), 8.27 (1H, s)

Mass spectrometric value (ESI-MS) 524 (M−1)

Compound 607 N-[3-(3-Fluoro-benzylidene-hydrazinocarbonyl)-4,5,6,7-tetrahydro-benzo[b]thiophen-2-yl]-3-(3-hydroxy-propylsulfanylmethyl)-benzamide

The title compound 607 was produced in substantially the same manner as in Example 8.

¹H-NMR (CD₃OD, 400 MHz): δ 1.77 (2H, m), 1.90 (4H, m), 2.51 (2H, t, J=7.3 Hz), 2.77 (2H, m), 2.86 (2H, bs), 3.63 (2H, m), 3.82 (2H, s), 7.17 (1H, dd, J=8.0 Hz, J=8.0 Hz), 7.55 (5H, m), 7.84 (1H, d, J=7.1 Hz), 7.92 (1H, s), 8.27 (1H, s)

Mass spectrometric value (ESI-MS) 524 (M−1)

Compound 608 N-[3-(4-Chloro-3-trifluoromethyl-benzylidene-hydrazinocarbonyl)-4,5,6,7-tetrahydro-benzo[b]thiophen-2-yl]-3-(3-hydroxy-propylsulfanylmethyl)-benzamide

The title compound 608 was produced in substantially the same manner as in Example 8.

¹H-NMR (CD₃OD, 400 MHz): δ 1.77 (2H, m), 1.90 (4H, m), 2.51 (2H, m), 2.76 (2H, m), 2.86 (2H, m), 3.60 (2H, m), 3.83 (2H, s), 7.52 (1H, m), 7.62 (1H, m), 7.68 (1H, m), 7.75-8.08 (4H, m), 8.32 (1H, s)

Mass spectrometric value (ESI-MS) 608 (M−1)

Compound 609 3-{[(2-Diethylamino-ethyl)-methyl-amino]-methyl}-N-[3-(3,4-dimethyl-benzylidene-hydrazinocarbonyl)-4,5,6,7-tetrahydro-benzo[b]thiophen-2-yl]-benzamide

The title compound 609 was produced in substantially the same manner as in Example 8.

¹H-NMR (CDCl₃, 400 MHz): δ 1.08 (6H, t, J=7.2 Hz), 1.85 (4H, m), 2.24 (3H, s), 2.29 (6H, s), 2.75 (12H, m), 3.62 (2H, s), 7.17 (1H, d, J=7.6 Hz), 7.44 (2H, dd, J=15.0 Hz, J=7.6 Hz), 7.55 (2H, d, J=7.6 Hz), 7.63 (2H, s), 7.95 (2H, m), 8.06 (1H, s)

Mass spectrometric value (ESI-MS) 572 (M−1)

Compound 610 3-{[(2-Diethylamino-ethyl)-methyl-amino]-methyl}-N-[3-(4-methyl-benzylidene-hydrazinocarbonyl)-4,5,6,7-tetrahydro-benzo-[b]thiophen-2-yl]-benzamide

The title compound 610 was produced in substantially the same manner as in Example 8.

¹H-NMR (CDCl₃, 400 MHz): δ 1.08 (6H, t, J=7.1 Hz), 1.85 (4H, m), 2.24 (3H, s), 2.37 (3H, s), 2.74 (12H, m), 3.61 (2H, s), 7.20 (2H, d, J=8.0 Hz), 7.44 (1H, dd, J=15.9 Hz, J=8.1 Hz), 7.54 (1H, d, J=7.8 Hz), 7.66 (2H, d, J=8.0 Hz), 7.95 (2H, m), 8.12 (1H, s)

Mass spectrometric value (ESI-MS) 558 (M−1)

Compound 611 3-{[(2-Diethylamino-ethyl)-methyl-amino]-methyl}-N-[3-(4-fluoro-benzylidene-hydrazinocarbonyl)-4,5,6,7-tetrahydro-benzo-[b]thiophen-2-yl]-benzamide

The title compound 611 was produced in substantially the same manner as in Example 8.

¹H-NMR (CDCl₃, 400 MHz): δ 1.10 (6H, t, J=7.3 Hz), 1.83 (4H, m), 2.24 (3H, s), 2.75 (12H, m), 3.61 (2H, s), 7.09 (2H, dd, J=8.6 Hz, J=8.6 Hz), 7.44 (1H, dd, J=15.1 Hz, J=7.6 Hz), 7.54 (1H, d, J=7.6 Hz), 7.76 (2H, m), 7.93 (2H, m), 8.16 (1H, s)

Mass spectrometric value (ESI-MS) 562 (M−1)

Compound 612 3-{[(2-Diethylamino-ethyl)-methyl-amino]-methyl}-N-[3-(3-fluoro-benzylidene-hydrazinocarbonyl)-4,5,6,7-tetrahydro-benzo-[b]thiophen-2-yl]-benzamide

The title compound 612 was produced in substantially the same manner as in Example 8.

¹H-NMR (CDCl₃, 400 MHz): δ 1.11 (6H, t, J=7.2 Hz), 1.81 (4H, m), 2.23 (3H, s), 2.77 (12H, m), 3.61 (2H, s), 7.08 (1H, m), 7.31-7.59 (4H, m), 7.91 (2H, m), 8.21 (1H, s)

Mass spectrometric value (ESI-MS) 562 (M−1)

Compound 613 N-[3-(4-Chloro-3-trifluoromethyl-benzylidene-hydrazinocarbonyl)-4,5,6,7-tetrahydro-benzo[b]thiophen-2-yl]-3-{[(2-diethylamino-ethyl)-methyl-amino]-methyl}-benzamide

The title compound 613 was produced in substantially the same manner as in Example 8.

¹H-NMR (CDCl₃, 400 MHz): δ 1.10 (6H, m), 1.91 (4H, m), 2.25 (3H, s), 2.55-2.80 (12H, m), 3.63 (2H, s), 7.46 (1H, m), 7.57 (2H, d, 8.3 Hz), 7.94 (3H, m), 8.04 (1H, m), 8.23 (1H, s)

Mass spectrometric value (ESI-MS) 646 (M−1)

Compound 614 3-{[(2-Diethylamino-ethyl)-methyl-amino]-methyl}-N-[3-(4-methoxy-benzylidene-hydrazinocarbonyl)-4,5,6,7-tetrahydro-benzo-[b]thiophen-2-yl]-benzamide

The title compound 614 was produced in substantially the same manner as in Example 8.

¹H-NMR (CDCl₃, 400 MHz): δ 1.04 (6H, t, J=7.1 Hz), 1.83 (4H, m), 2.23 (3H, s), 2.68 (12H, m), 3.60 (2H, s), 3.82 (3H, s), 6.89 (2H, d, J=8.8 Hz), 7.45 (1H, dd, J=15.4 Hz, J=7.6 Hz), 7.56 (1H, d, J=7.6 Hz), 7.70 (2H, d, J=8.8 Hz), 7.82-8.02 (2H, m), 8.09 (1H, s)

Mass spectrometric value (ESI-MS) 574 (M−1)

Compound 615 3-[1,4′]Bipiperidinyl-1′-ylmethyl-N-[3-(3,4-dimethyl-benzylidene-hydrazinocarbonyl)-4,5,6,7-tetrahydro-benzo[b]thiophen-2-yl]-benzamide

The title compound 615 was produced in substantially the same manner as in Example 8.

¹H-NMR (CDCl₃, 400 MHz): δ 1.46 (2H, bs), 1.68-2.06 (15H, m), 2.27 (6H, s), 2.60-3.02 (10H, m), 3.54 (2H, s), 7.14 (1H, m), 7.46 (3H, m), 7.60 (1H, s), 7.94 (2H, m), 8.11 (1H, s)

Mass spectrometric value (ESI-MS) 610 (M−1)

Compound 616 3-[1,4′]Bipiperidinyl-1′-ylmethyl-N-[3-(4-methyl-benzylidene-hydrazinocarbonyl)-4,5,6,7-tetrahydro-benzo[b]thiophen-2-yl]-benzamide

The title compound 616 was produced in substantially the same manner as in Example 8.

¹H-NMR (CDCl₃, 400 MHz): δ 1.47 (2H, bs), 1.68-2.08 (14H, m), 2.37 (3H, s), 2.65-3.00 (11H, m), 3.54 (2H, s), 7.20 (2H, d, J=7.8 Hz), 7.45 (2H, m), 7.66 (2H, d, J=7.8 Hz), 7.90 (2H, m), 8.16 (1H, s)

Mass spectrometric value (ESI-MS) 596 (M−1)

Compound 617 3-[1,4′]Bipiperidinyl-1′-ylmethyl-N-[3-(4-fluoro-benzylidene-hydrazinocarbonyl)-4,5,6,7-tetrahydro-benzo[b]thiophen-2-yl]-benzamide

The title compound 617 was produced in substantially the same manner as in Example 8.

¹H-NMR (CDCl₃, 400 MHz): δ 1.48 (2H, bs), 1.65-2.10 (14H, m), 2.74 (7H, m), 2.87 (2H, m), 2.94 (2H, m), 3.55 (2H, s), 7.10 (2H, dd, J=8.6 Hz, J=8.6 Hz), 7.46 (2H, m), 7.77 (2H, m), 7.92 (1H, d, J=7.6 Hz), 7.97 (1H, s), 8.18 (1H, s)

Mass spectrometric value (ESI-MS) 600 (M−1)

Compound 618 3-[1,4′]Bipiperidinyl-1′-ylmethyl-N-[3-(3-fluoro-benzylidene-hydrazinocarbonyl)-4,5,6,7-tetrahydro-benzo[b]thiophen-2-yl]-benzamide

The title compound 618 was produced in substantially the same manner as in Example 8.

¹H-NMR (CDCl₃, 400 MHz): δ 1.48 (2H, bs), 1.70-2.08 (14H, m), 2.86 (11H, m), 3.55 (2H, s), 7.10 (1H, ddd, J=8.3 Hz, J=8.3 Hz, J=2.4 Hz), 7.50 (5H, m), 7.91 (1H, d, J=7.6 Hz), 7.97 (1H, s), 8.20 (1H, s)

Mass spectrometric value (ESI-MS) 600 (M−1)

Compound 619 3-[1,4′]Bipiperidinyl-1′-ylmethyl-N-[3-(4-chloro-3-trifluoromethyl-benzylidene-hydrazinocarbonyl)-4,5,6,7-tetrahydro-benzo[b]thiophen-2-yl]-benzamide

The title compound 619 was produced in substantially the same manner as in Example 8.

¹H-NMR (CDCl₃, 400 MHz): δ 1.47 (2H, bs), 1.86 (14H, m), 2.84 (11H, m), 3.53 (2H, s), 7.48 (3H, m), 7.91 (3H, m), 8.01 (1H, s), 8.31 (1H, s)

Mass spectrometric value (ESI-MS) 684 (M−1)

Compound 620 3-[1,4′]Bipiperidinyl-1′-ylmethyl-N-[3-(4-methoxy-benzylidene-hydrazinocarbonyl)-4,5,6,7-tetrahydro-benzo[b]thiophen-2-yl]-benzamide

The title compound 620 was produced in substantially the same manner as in Example 8.

¹H-NMR (CDCl₃, 400 MHz): δ 1.47 (2H, bs), 1.85 (14H, m), 2.82 (11H, m), 3.53 (2H, bs), 3.82 (3H, m), 6.90 (2H, m), 7.43 (2H, m), 7.69 (2H, d, J=7.1 Hz), 7.91 (2H, m), 8.15 (1H, s)

Mass spectrometric value (ESI-MS) 612 (M−1)

Compound 621 N-[3-(3,4-Dimethyl-benzylidene-hydrazinocarbonyl)-4,5,6,7-tetrahydro-benzo[b]thiophen-2-yl]-3-[4-(2-hydroxy-ethyl)-piperazin-1-ylmethyl]-benzamide

The title compound 621 was produced in substantially the same manner as in Example 8.

¹H-NMR (CDCl₃, 400 MHz): δ 1.87 (4H, m), 2.29 (6H, s), 2.55 (10H, m), 2.72 (2H, m), 2.86 (2H, m), 3.60 (4H, m), 7.16 (1H, d, J=7.6 Hz), 7.43 (2H, m), 7.54 (1H, d, J=7.8 Hz), 7.62 (1H, s), 7.93 (1H, d, J=7.8 Hz), 8.00 (1H, s), 8.05 (1H, s)

Mass spectrometric value (ESI-MS) 572 (M−1)

Compound 622 3-[4-(2-Hydroxy-ethyl)-piperazin-1-ylmethyl]-N-[3-(4-methyl-benzyl idene-hydrazinocarbonyl)-4,5,6,7-tetrahydro-benzo-[b]thiophen-2-yl]-benzamide

The title compound 622 was produced in substantially the same manner as in Example 8.

¹H-NMR (CDCl₃, 400 MHz): δ 1.85 (4H, m), 2.37 (3H, s), 2.54 (10H, m), 2.71 (2H, m), 2.85 (2H, m), 3.60 (4H, m), 7.20 (2H, d, J=7.8 Hz), 7.43 (1H, dd, J=7.8 Hz, J=7.8 Hz), 7.54 (1H, d, J=7.8 Hz), 7.66 (2H, d, J=7.8 Hz), 7.92 (1H, d, J=7.8 Hz), 8.00 (1H, s), 8.10 (1H, s)

Mass spectrometric value (ESI-MS) 558 (M−1)

Compound 623 N-[3-(4-Fluoro-benzylidene-hydrazinocarbonyl)-4,5,6,7-tetrahydro-benzo[b]thiophen-2-yl]-3-[4-(2-hydroxy-ethyl)-piperazin-1-ylmethyl]-benzamide

The title compound 623 was produced in substantially the same manner as in Example 8.

¹H-NMR (CDCl₃, 400 MHz): δ 1.87 (4H, m), 2.54 (10H, m), 2.73 (2H, m), 2.86 (2H, m), 3.60 (4H, m), 7.11 (2H, dd, J=8.7 Hz, J=8.7 Hz), 7.44 (1H, dd, J=7.6 Hz, J=7.6 Hz), 7.54 (1H, d, J=7.6 Hz), 7.79 (2H, m), 7.92 (1H, m), 8.00 (1H, s), 8.12 (1H, s)

Mass spectrometric value (ESI-MS) 562 (M−1)

Compound 624 N-[3-(3-Fluoro-benzylidene-hydrazinocarbonyl)-4,5,6,7-tetrahydro-benzo[b]thiophen-2-yl]-3-[4-(2-hydroxy-ethyl)-piperazin-1-ylmethyl]-benzamide

The title compound 624 was produced in substantially the same manner as in Example 8.

¹H-NMR (CDCl₃, 400 MHz): δ 1.87 (4H, m), 2.54 (10H, m), 2.72 (2H, m), 2.84 (2H, m), 3.60 (4H, m), 7.11 (1H, ddd, J=8.3 Hz, J=8.3 Hz, J=2.4 Hz), 7.45 (5H, m), 7.92 (1H, d, J=7.6 Hz), 8.00 (1H, s), 8.14 (1H, s)

Mass spectrometric value (ESI-MS) 562 (M−1)

Compound 625 N-[3-(4-Chloro-3-trifluoromethyl-benzylidene-hydrazinocarbonyl)-4,5,6,7-tetrahydro-benzo[b]thiophen-2-yl]-3-[4-(2-hydroxy-ethyl)-piperazin-1-ylmethyl]-benzamide

The title compound 625 was produced in substantially the same manner as in Example 8.

¹H-NMR (CDCl₃, 400 MHz): δ 1.83 (4H, m), 2.53 (10H, m), 2.69 (2H, m), 2.82 (2H, m), 3.60 (4H, m), 7.44 (1H, dd, J=7.7 Hz, J=7.7 Hz), 7.54 (2H, d, J=8.3 Hz), 7.92 (2H, m), 7.98 (1H, s), 8.01 (1H, s), 8.22 (1H, s)

Mass spectrometric value (ESI-MS) 646 (M−1)

Compound 626 3-[4-(2-Hydroxy-ethyl)-piperazin-1-ylmethyl]-N-[3-(4-methoxy-benzylidene-hydrazinocarbonyl)-4,5,6,7-tetrahydro-benzo-[b]thiophen-2-yl]-benzamide

The title compound 626 was produced in substantially the same manner as in Example 8.

¹H-NMR (CDCl₃, 400 MHz): δ 1.85 (4H, m), 2.53 (10H, m), 2.70 (2H, m), 2.84 (2H, m), 3.59 (4H, m), 3.83 (3H, s), 6.90 (2H, d, J=8.8 Hz), 7.42 (1H, dd, J=7.8 Hz, J=7.8 Hz), 7.53 (1H, d, J=7.8 Hz), 7.72 (2H, d, J=8.8 Hz), 7.92 (1H, d, J=7.8 Hz), 7.99 (1H, s), 8.07 (1H, s)

Mass spectrometric value (ESI-MS) 574 (M−1)

Compound 627 3-{[Bis-(2-hydroxy-propyl)-amino]-methyl}-N-[3-(3,4-dimethyl-benzylidene-hydrazinocarbonyl)-4,5,6,7-tetrahydro-benzo-[b]thiophen-2-yl]-benzamide

The title compound 627 was produced in substantially the same manner as in Example 8.

¹H-NMR (CDCl₃, 400 MHz): δ 1.14 (6H, m), 1.84 (4H, m), 2.25 (6H, m), 2.50 (2H, d, J=5.6 Hz), 2.62 (2H, m), 2.70 (2H, m), 2.83 (2H, m), 3.81-4.06 (4H, m), 7.08 (1H, m), 7.46 (3H, m), 7.60 (1H, s), 8.02 (2H, m), 8.20 (1H, bs)

Mass spectrometric value (ESI-MS) 575 (M−1)

Compound 628 3-{[Bis-(2-hydroxy-propyl)-amino]-methyl}-N-[3-(4-methyl-benzylidene-hydrazinocarbonyl)-4,5,6,7-tetrahydro-benzo-[b]thiophen-2-yl]-benzamide

The title compound 628 was produced in substantially the same manner as in Example 8.

¹H-NMR (CDCl₃, 400 MHz): δ 1.13 (6H, m), 1.87 (4H, m), 2.37 (3H, m), 2.50 (2H, d, J=5.6 Hz), 2.62 (2H, m), 2.71 (2H, m), 2.84 (2H, m), 3.93 (4H, m), 7.16 (2H, m), 7.44 (2H, m), 7.70 (2H, m), 8.00 (2H, m), 8.22 (1H, bs)

Mass spectrometric value (ESI-MS) 561 (M−1)

Compound 629 3-{[Bis-(2-hydroxy-propyl)-amino]-methyl}-N-[3-(4-fluoro-benzylidene-hydrazinocarbonyl)-4,5,6,7-tetrahydro-benzo[b]thiophen-2-yl]-benzamide

The title compound 629 was produced in substantially the same manner as in Example 8.

¹H-NMR (CDCl₃, 400 MHz): δ 1.12 (6H, t, J=6.1 Hz), 1.88 (4H, m), 2.50 (2H, m), 2.63 (2H, m), 2.73 (2H, m), 2.84 (2H, m), 3.94 (4H, m), 7.06 (2H, dd, J=8.6 Hz, J=8.6 Hz), 7.44 (2H, m), 7.85 (2H, m), 8.05 (2H, m), 8.25 (1H, d, J=6.8 Hz)

Mass spectrometric value (ESI-MS) 565 (M−1)

Compound 630 3-{[Bis-(2-hydroxy-propyl)-amino]-methyl}-N-[3-(3-fluoro-benzylidene-hydrazinocarbonyl)-4,5,6,7-tetrahydro-benzo[b]thiophen-2-yl]-benzamide

The title compound 630 was produced in substantially the same manner as in Example 8.

¹H-NMR (CDCl₃, 400 MHz): δ 1.14 (6H, t, J=6.1 Hz), 1.84 (4H, m), 2.51 (2H, m), 2.66 (4H, m), 2.83 (2H, m), 3.95 (4H, m), 7.00 (1H, m), 7.23 (1H, m), 7.42 (3H, m), 7.72 (1H, m), 8.03 (1H, m), 8.18 (1H, s), 8.27 (1H, d, J=10.3 Hz)

Mass spectrometric value (ESI-MS) 565 (M−1)

Compound 631 3-{[Bis-(2-hydroxy-propyl)-amino]-methyl}-N-[3-(4-chloro-3-trifluoromethyl-benzylidene-hydrazinocarbonyl)-4,5,6,7-tetrahydro-benzo[b]thiophen-2-yl]-benzamide

The title compound 631 was produced in substantially the same manner as in Example 8.

¹H-NMR (CDCl₃, 400 MHz): δ 1.12 (6H, m), 1.72 (4H, m), 2.52 (2H, d, J=6.1 Hz), 2.68 (6H, m), 3.97 (4H, m), 7.32 (1H, d, J=8.3 Hz), 7.43 (2H, m), 7.87 (1H, m), 8.01 (2H, m), 8.30 (1H, s), 8.33 (1H, s)

Mass spectrometric value (ESI-MS) 649 (M−1)

Compound 632 3-{[Bis-(2-hydroxy-propyl)-amino]-methyl}-N-[3-(4-methoxy-benzylidene-hydrazinocarbonyl)-4,5,6,7-tetrahydro-benzo-[b]thiophen-2-yl]-benzamide

The title compound 632 was produced in substantially the same manner as in Example 8.

¹H-NMR (CDCl₃, 400 MHz): δ 1.13 (6H, m), 1.86 (4H, m), 2.49 (2H, m), 2.62 (2H, m), 2.70 (2H, m), 2.81 (2H, m), 3.75-4.05 (7H, m), 6.82 (2H, m), 7.42 (2H, m), 7.74 (2H, m), 8.01 (1H, m), 8.06 (1H, s), 8.23 (1H, m)

Mass spectrometric value (ESI-MS) 577 (M−1)

Compound 633 N-[3-(3,4-Dimethyl-benzylidene-hydrazinocarbonyl)-4,5,6,7-tetrahydro-benzo[b]thiophen-2-yl]-3-(4-hydroxy-piperidin-1-ylmethyl)-benzamide

The title compound 633 was produced in substantially the same manner as in Example 8.

¹H-NMR (CDCl₃, 400 MHz): δ 1.64 (2H, m), 1.85 (6H, m), 2.25 (8H, m), 2.75 (6H, m), 3.63 (2H, s), 3.70 (1H, m), 7.15 (1H, d, J=7.8 Hz), 7.43 (2H, m), 7.56 (1H, m), 7.61 (1H, s), 7.93 (1H, d, J=7.8 Hz), 7.98 (1H, s), 8.06 (1H, s)

Mass spectrometric value (ESI-MS) 543 (M−1)

Compound 634 3-(4-Hydroxy-piperidin-1-ylmethyl)-N-[3-(4-methyl-benzylidene-hydrazinocarbonyl)-4,5,6,7-tetrahydro-benzo[b]thiophen-2-yl]-benzamide

The title compound 634 was produced in substantially the same manner as in Example 8.

¹H-NMR (CDCl₃, 400 MHz): δ 1.64 (2H, m), 1.86 (6H, m), 2.26 (2H, t, J=9.5 Hz), 2.37 (3H, s), 2.71 (2H, m), 2.81 (4H, m), 3.64 (2H, s), 3.72 (1H, m), 7.19 (2H, d, J=7.9 Hz), 7.43 (1H, dd, J=7.8 Hz), 7.57 (1H, d, J=7.8 Hz), 7.66 (2H, d, J=7.9 Hz), 7.94 (2H, m), 8.09 (1H, s)

Mass spectrometric value (ESI-MS) 529 (M−1)

Compound 635 N-[3-(4-Fluoro-benzylidene-hydrazinocarbonyl)-4,5,6,7-tetrahydro-benzo[b]thiophen-2-yl]-3-(4-hydroxy-piperidin-1-ylmethyl)-benzamide

The title compound 635 was produced in substantially the same manner as in Example 8.

¹H-NMR (CDCl₃, 400 MHz): δ 1.64 (2H, m), 1.90 (6H, m), 2.23 (2H, m), 2.80 (6H, m), 3.62 (2H, s), 3.73 (1H, m), 7.11 (2H, dd, J=8.6 Hz, J=8.6 Hz), 7.45 (1H, m), 7.58 (1H, m), 7.79 (2H, dd, J=8.6 Hz, J=8.6 Hz), 7.94 (1H, d, J=7.8 Hz), 7.99 (1H, s), 8.12 (1H, s)

Mass spectrometric value (ESI-MS) 533 (M−1)

Compound 636 N-[3-(3-Fluoro-benzylidene-hydrazinocarbonyl)-4,5,6,7-tetrahydro-benzo[b]thiophen-2-yl]-3-(4-hydroxy-piperidin-1-ylmethyl)-benzamide

The title compound 636 was produced in substantially the same manner as in Example 8.

¹H-NMR (CDCl₃, 400 MHz): δ 1.69 (2H, m), 1.90 (6H, m), 2.42 (2H, bs), 2.78 (6H, m), 3.75 (3H, m), 7.11 (1H, m), 7.30-7.80 (5H, m), 7.98 (2H, m), 8.14 (1H, s)

Mass spectrometric value (ESI-MS) 533 (M−1)

Compound 637 N-[3-(4-Chloro-3-trifluoromethyl-benzylidene-hydrazinocarbonyl)-4,5,6,7-tetrahydro-benzo[b]thiophen-2-yl]-3-(4-hydroxy-piperidin-1-ylmethyl)-benzamide

The title compound 637 was produced in substantially the same manner as in Example 8.

¹H-NMR (CDCl₃, 400 MHz): δ 1.63 (2H, m), 1.85 (6H, m), 2.19 (2H, m), 2.74 (6H, m), 3.58 (2H, s), 3.71 (1H, m), 7.44 (1H, dd, J=7.6 Hz, J=7.6 Hz), 7.54 (2H, m), 7.94 (4H, m), 8.23 (1H, s)

Mass spectrometric value (ESI-MS) 617 (M−1)

Compound 638 3-(4-Hydroxy-piperidin-1-ylmethyl)-N-[3-(4-methoxy-benzylidene-hydrazinocarbonyl)-4,5,6,7-tetrahydro-benzo[b]thiophen-2-yl]-benzamide

The title compound 638 was produced in substantially the same manner as in Example 8.

¹H-NMR (CDCl₃, 400 MHz): δ 1.62 (2H, m), 1.87 (6H, m), 2.19 (2H, m), 2.77 (6H, m), 3.59 (2H, s), 3.70 (1H, m), 3.83 (3H, s), 6.90 (2H, d, J=8.5 Hz), 7.43 (1H, dd, J=7.6 Hz, J=7.6 Hz), 7.55 (1H, d, J=7.6 Hz), 7.72 (2H, d, J=8.5 Hz), 7.92 (1H, d, J=7.6 Hz), 7.98 (1H, s), 8.06 (1H, s)

Mass spectrometric value (ESI-MS) 545 (M−1)

Compound 639 N-[3-(3,4-Dimethyl-benzylidene-hydrazinocarbonyl)-4,5,6,7-tetrahydro-benzo[b]thiophen-2-yl]-3-(4-hydroxymethyl-piperidin-1-ylmethyl)-benzamide

The title compound 639 was produced in substantially the same manner as in Example 8.

¹H-NMR (CDCl₃, 400 MHz): δ 1.37 (2H, m), 1.49 (1H, m), 1.71 (2H, m), 1.86 (4H, m), 2.04 (2H, m), 2.29 (6H, s), 2.73 (2H, m), 2.86 (2H, m), 2.93 (2H, m), 3.49 (2H, d, J=6.3 Hz), 3.62 (2H, s), 7.16 (1H, d, J=7.8 Hz), 7.45 (2H, m), 7.58 (1H, m), 7.63 (1H, s), 7.94 (1H, d, J=7.8 Hz), 7.99 (1H, s), 8.05 (1H, s)

Mass spectrometric value (ESI-MS) 557 (M−1)

Compound 640 3-(4-Hydroxymethyl-piperidin-1-ylmethyl)-N-[3-(4-methyl-benzylidene-hydrazinocarbonyl)-4,5,6,7-tetrahydro-benzo[b]thiophen-2-yl]-benzamide

The title compound 640 was produced in substantially the same manner as in Example 8.

¹H-NMR (CDCl₃, 400 MHz): δ 1.40 (2H, m), 1.50 (1H, m), 1.71 (2H, m), 1.89 (4H, m), 2.06 (2H, m), 2.38 (3H, m), 2.73 (2H, m), 2.86 (2H, m), 2.95 (2H, m), 3.49 (2H, d, J=6.1 Hz), 3.63 (2H, s), 7.21 (2H, d, J=8.0 Hz), 7.45 (1H, dd, J=7.7 Hz, J=14.9 Hz), 7.59 (1H, d, J=7.6 Hz), 7.68 (2H, d, J=8.0 Hz), 7.97 (2H, m), 8.09 (1H, s)

Mass spectrometric value (ESI-MS) 543 (M−1)

Compound 641 N-[3-(4-Fluoro-benzylidene-hydrazinocarbonyl)-4,5,6,7-tetrahydro-benzo[b]thiophen-2-yl]-3-(4-hydroxymethyl-piperidin-1-ylmethyl)-benzamide

The title compound 641 was produced in substantially the same manner as in Example 8.

¹H-NMR (CDCl₃, 400 MHz): δ 1.34 (2H, m), 1.50 (1H, m), 1.69 (2H, m), 1.84 (4H, m), 2.01 (2H, m), 2.71 (2H, m), 2.87 (4H, m), 3.49 (2H, d, J=6.4 Hz), 3.58 (2H, s), 7.10 (2H, dd, J=8.5 Hz), 7.43 (1H, m), 7.55 (1H, m), 7.78 (2H, m), 7.91 (1H, m), 7.98 (1H, bs), 8.13 (1H, s)

Mass spectrometric value (ESI-MS) 547 (M−1)

Compound 642 N-[3-(3-Fluoro-benzylidene-hydrazinocarbonyl)-4,5,6,7-tetrahydro-benzo[b]thiophen-2-yl]-3-(4-hydroxymethyl-piperidin-1-ylmethyl)-benzamide

The title compound 642 was produced in substantially the same manner as in Example 8.

¹H-NMR (CDCl₃, 400 MHz): δ 1.35 (2H, m), 1.51 (1H, m), 1.70 (2H, m), 1.84 (4H, m), 2.01 (2H, m), 2.70 (2H, m), 2.83 (2H, m), 2.90 (2H, m), 3, 49 (2H, d, J=6.3 Hz), 3.58 (2H, s), 7.10 (1H, ddd, J=8.3 Hz, J=8.3 Hz, J=2.7 Hz), 7.45 (5H, m), 7.90 (1H, d, J=7.4 Hz), 7.98 (1H, s), 8.14 (1H, s)

Mass spectrometric value (ESI-MS) 547 (M−1)

Compound 643 N-[3-(4-Chloro-3-trifluoromethyl-benzylidene-hydrazinocarbonyl)-4,5,6,7-tetrahydro-benzo[b]thiophen-2-yl]-3-(4-hydroxymethyl-piperidin-1-ylmethyl)-benzamide

The title compound 643 was produced in substantially the same manner as in Example 8.

¹H-NMR (CDCl₃, 400 MHz): δ 1.39 (2H, m), 1.52 (1H, m), 1.72 (2H, m), 1.88 (4H, m), 2.05 (2H, m), 2.66-2.98 (6H, m), 3.50 (2H, d, J=6.1 Hz), 3.61 (2H, s), 7.46 (1H, m), 7.57 (1H, m), 7.86 (1H, m), 7.96 (3H, m), 8.04 (1H, s), 8.21 (1H, s)

Mass spectrometric value (ESI-MS) 631 (M−1)

Compound 644 3-(4-Hydroxymethyl-piperidin-1-ylmethyl)-N-[3-(4-methoxy-benzylidene-hydrazinocarbonyl)-4,5,6,7-tetrahydro-benzo-[b]thiophen-2-yl]-benzamide

The title compound 644 was produced in substantially the same manner as in Example 8.

¹H-NMR (CDCl₃, 400 MHz): δ 1.34 (2H, m), 1.49 (1H, m), 1.69 (2H, m), 1.84 (4H, m), 2.00 (2H, m), 2.69 (2H, m), 2.81 (2H, m), 2.88 (2H, m), 3.48 (2H, d, J=6.4 Hz), 3.57 (2H, s), 3.83 (3H, s), 6.90 (2H, d, J=8.8 Hz), 7.43 (1H, m), 7.55 (1H, m), 7.70 (2H, d, J=8.8 Hz), 7.91 (1H, d, J=7.8 Hz), 7.97 (1H, m), 8.07 (1H, s)

Mass spectrometric value (ESI-MS) 559 (M−1)

Compound 645 N-{3-[N′-(3,4-Dimethyl-benzyl)-hydrazinocarbonyl]-4-methyl-thiophen-2-yl}-3-(3-hydroxy-propylsulfanylmethyl)-benzamide

The title compound 645 was produced in substantially the same manner as in Example 8.

¹H-NMR (CDCl₃, 400 MHz): δ 1.87 (2H, m), 2.26 (9H, m), 2.56 (2H, m), 3.73 (2H, m), 3.82 (2H, s), 4.06 (2H, s), 6.46 (1H, s), 7.13 (1H, bs), 7.18 (1H, bs), 7.50 (1H, m), 7.57 (1H, d, J=7.8 Hz), 7.93 (2H, m), 13.00 (1H, s)

Mass spectrometric value (ESI-MS) 496 (M−1)

Compound 646 3-[(3,4-Dimethyl-benzylidene-)-amino]-2-[3-(1H-[1,2,4]triazol-3-ylsulfanylmethyl)-phenyl]-5,6,7,8-tetrahydro-3H-benzo[4,5]thieno[2,3-d]pyrimidin-4-one

The title compound 646 was produced in substantially the same manner as in Example 8.

¹H-NMR (CDCl₃, 400 MHz): δ 1.88 (4H, m), 2.31 (3H, s), 2.33 (3H, s), 2.80 (2H, m), 3.05 (2H, m), 4.33 (2H, s), 7.10-7.88 (7H, m), 8.03 (1H, s), 8.76 (1H, s)

Mass spectrometric value (ESI-MS) 525 (M−1)

Compound 647 3-[(4-Methyl-benzylidene-)-amino]-2-[3-(1H-[1,2,4]triazol-3-ylsulfanylmethyl)-phenyl]-5,6,7,8-tetrahydro-3H-benzo[4,5]thieno[2,3-d]pyrimidin-4-one

The title compound 647 was produced in substantially the same manner as in Example 8.

¹H-NMR (CDCl₃, 400 MHz): δ 1.88 (4H, m), 2.35 (3H, s), 2.80 (2H, m), 3.05 (2H, m), 4.34 (2H, s), 7.17 (2H, d, J=7.8 Hz), 7.26 (1H, m), 7.37 (1H, m), 7.56 (2H, m), 7.76 (1H, s), 8.00 (2H, m), 8.81 (1H, s)

Mass spectrometric value (ESI-MS) 511 (M−1)

Compound 648 3-[(4-Fluoro-benzylidene-)-amino]-2-[3-(1H-[1,2,4]triazol-3-ylsulfanylmethyl)-phenyl]-5,6,7,8-tetrahydro-3H-benzo[4,5]thieno[2,3-d]pyrimidin-4-one

The title compound 648 was produced in substantially the same manner as in Example 8.

¹H-NMR (CDCl₃, 400 MHz): δ 1.89 (4H, m), 2.81 (2H, m), 3.05 (2H, m), 4.36 (2H, s), 7.08 (2H, dd, J=8.7 Hz), 7.31 (1H, m), 7.40 (1H, d, J=7.8 Hz), 7.56 (1H, d, J=7.8 Hz), 7.69 (2H, m), 7.76 (1H, m), 8.04 (1H, s), 8.92 (1H, s)

Mass spectrometric value (ESI-MS) 515 (M−1)

Compound 649 3-[(3-Fluoro-benzylidene)-amino]-2-[3-(1H-[1,2,4]triazol-3-ylsulfanylmethyl)-phenyl]-5,6,7,8-tetrahydro-3H-benzo[4,5]thieno[2,3-d]pyrimidin-4-one

The title compound 649 was produced in substantially the same manner as in Example 8.

¹H-NMR (CDCl₃, 400 MHz): δ 1.89 (4H, m), 2.81 (2H, m), 3.05 (2H, m), 4.36 (2H, s), 7.15 (1H, m), 7.36 (5H, m), 7.55 (1H, m), 7.75 (1H, m), 8.03 (1H, s), 9.01 (1H, s)

Mass spectrometric value (ESI-MS) 515 (M−1)

Compound 650 3-[(4-Chloro-3-trifluoromethyl-benzylidene)-amino]-2-[3-(1H-[1,2,4]triazol-3-ylsulfanylmethyl)-phenyl]-5,6,7,8-tetrahydro-3H-benzo[4,5]thieno[2,3-d]pyrimidin-4-one

The title compound 650 was produced in substantially the same manner as in Example 8.

¹H-NMR (CDCl₃, 400 MHz): δ 1.89 (4H, m), 2.68 (2H, m), 2.81 (2H, m), 4.37 (2H, s), 7.30-8.02 (7H, m), 8.06 (1H, m), 9.17 (1H, s)

Mass spectrometric value (ESI-MS) 599 (M−1)

Compound 651 3-[(4-Methoxy-benzylidene)-amino]-2-[3-(1H-[1,2,4]triazol-3-ylsulfanylmethyl)-phenyl]-5,6,7,8-tetrahydro-3H-benzo[4,5]thieno[2,3-d]pyrimidin-4-one

The title compound 651 was produced in substantially the same manner as in Example 8.

¹H-NMR (CDCl₃, 400 MHz): δ 1.88 (4H, m), 2.80 (2H, m), 3.05 (2H, m), 3.81 (3H, s), 4.33 (2H, s), 6.87 (2H, d, J=8.8 Hz), 7.28 (1H, m), 7.55 (1H, m), 7.61 (2H, d, J=8.8 Hz), 7.76 (1H, m), 8.00 (1H, s), 8.73 (1H, s), 9.15 (1H, s)

Mass spectrometric value (ESI-MS) 527 (M−1)

Example 9 Compound 652 3-{[Acetyl-(2-diethylamino-ethyl)-amino]-methyl}-N-[3-(3,4-dimethyl-benzylidene-hydrazinocarbonyl)-4,5,6,7-tetrahydro-benzo[b]thiophen-2-yl]-benzamide

2-Amino-4,5,6,7-tetrahydrobenzothiophene-3-carboxylic acid ethyl ester (Compound A) (4.0 g) was dissolved in anhydrous methylene chloride (40.0 ml). Subsequently, pyridine (2.8 ml) and 3-(chloromethyl)benzoyl chloride (compound B) (3.0 ml) were added at 0° C., and the mixture was stirred at 0° C. for one hr. After the completion of the reaction, distilled water was added, and the mixture was subjected to separatory extraction with chloroform, and the organic layer was washed with saturated brine, was dried over sodium sulfate, and was then concentrated to give 2-(3-chloromethyl-benzoylamino)-4,5,6,7-tetrahydro-benzo[b]thiophene-3-carboxylic acid ethyl ester as a useful intermediate (7.42 g, yield 100%).

2-(3-Chloromethyl-benzoylamino)-4,5,6,7-tetrahydro-benzo[b]-thiophene-3-carboxylic acid ethyl ester (800 mg) produced by the above reaction was dissolved in anhydrous methylene chloride (5.0 ml). Triethylamine (580 μl) and N,N-diethylethylenediamine (compound B′) (464 mg) were added to the solution at room temperature, and the mixture was stirred at room temperature for 15 hr. After the completion of the reaction, water was added at room temperature, and the mixture was subjected to separatory extraction with chloroform. The organic layer was washed with saturated brine, was dried over sodium sulfate, and was then concentrated to give 2-{3-[(2-diethylamino-ethylamino)-methyl]-benzoylamino}-4,5,6,7-tetrahydro-benzo[b]thiophene-3-carboxylic acid ethyl ester as a crude useful intermediate (902 mg, yield 100%).

2-{3-[(2-Diethylamino-ethylamino)-methyl]-benzoylamino}-4,5,6,7-tetrahydro-benzo[b]thiophene-3-carboxylic acid ethyl ester produced by the above reaction was dissolved in ethanol (5.0 ml). Hydrazine monohydrate (2 ml) was added to the solution, and the mixture was heated under reflux with stirring for 15 hr. After the completion of the reaction, water was added at room temperature, and the mixture was subjected to separatory extraction with chloroform. The organic layer was washed with saturated brine, was dried over sodium sulfate, and was then concentrated to give 3-[(2-diethylamino-ethylamino)-methyl]-N-(3-hydrazinocarbonyl-4,5,6,7-tetrahydro-benzo[b]thiophen-2-yl)-benzamide as a hydrazine compound (464 mg, yield 52%).

3-[(2-Diethylamino-ethylamino)-methyl]-N-(3-hydrazinocarbonyl-4,5,6,7-tetrahydro-benzo[b]thiophen-2-yl)-benzamide (77 mg) was dissolved in anhydrous toluene (1.0 ml). Acetic acid (50.0 μl) and 3,4-dimethylbenzaldehyde (compound C) (55.0 μl) were added to the solution at room temperature, and the mixture was heated under reflux with stirring for 15 hr. After the completion of the reaction, the reaction product was purified by column chromatography eluted with a chloroform-methanol system to give the title compound 652 (58.4 mg, yield 58%).

¹H-NMR (CDCl₃, 400 MHz): δ 0.98 (6H, m), 1.85 (7H, m), 2.28 (6H, m), 2.45-2.90 (12H, m), 3.76 (2H, m), 7.14 (1H, m), 7.32-8.12 (7H, m)

Mass spectrometric value (ESI-MS) 600 (M−1)

Compound 653 3-{[Acetyl-(2-diethylamino-ethyl)-amino]-methyl}-N-[3-(4-methyl-benzylidene-hydrazinocarbonyl)-4,5,6,7-tetrahydro-benzo[b]-thiophen-2-yl]-benzamide

The title compound 653 was produced in substantially the same manner as in Example 9.

¹H-NMR (CDCl₃, 400 MHz): δ 0.98 (6H, m), 1.83 (7H, m), 2.38 (3H, s), 2.42-2.90 (12H, m), 3.75 (2H, m), 7.24 (2H, m), 7.40-8.15 (7H, m)

Mass spectrometric value (ESI-MS) 586 (M−1)

Compound 654 3-{[Acetyl-(2-diethylamino-ethyl)-amino]-methyl}-N-[3-(4-fluoro-benzylidene-hydrazinocarbonyl)-4,5,6,7-tetrahydro-benzo[b]-thiophen-2-yl]-benzamide

The title compound 654 was produced in substantially the same manner as in Example 9.

¹H-NMR (CDCl₃, 400 MHz): δ 0.93 (6H, m), 1.83 (7H, m), 2.48 (4H, m), 2.69 (6H, m), 2.80 (2H, m), 3.75 (2H, m), 7.06 (2H, m), 7.40-7.95 (6H, m), 8.09 (1H, s)

Mass spectrometric value (ESI-MS) 590 (M−1)

Compound 655 3-{[Acetyl-(2-diethylamino-ethyl)-amino]-methyl}-N-[3-(3-fluoro-benzylidene-hydrazinocarbonyl)-4,5,6,7-tetrahydro-benzo[b]-thiophen-2-yl]-benzamide

The title compound 655 was produced in substantially the same manner as in Example 9.

¹H-NMR (CDCl₃, 400 MHz): δ 0.94 (6H, m), 1.83 (7H, m), 2.62 (12H, m), 3.76 (2H, m), 7.08 (1H, m), 7.29-8.20 (8H, m)

Mass spectrometric value (ESI-MS) 590 (M−1)

Compound 656 3-{[Acetyl-(2-diethylamino-ethyl)-amino]-methyl}-N-[3-(4-chloro-3-trifluoromethyl-benzylidene-hydrazinocarbonyl)-4,5,6,7-tetrahydro-benzo[b]thiophen-2-yl]-benzamide

The title compound 656 was produced in substantially the same manner as in Example 9.

¹H-NMR (CDCl₃, 400 MHz): δ 0.93 (6H, m), 1.83 (7H, m), 2.62 (12H, m), 3.77 (2H, m), 7.40-8.30 (8H, m)

Mass spectrometric value (ESI-MS) 674 (M−1)

Compound 657 3-{[Acetyl-(2-diethylamino-ethyl)-amino]-methyl}-N-[3-(4-methoxy-benzylidene-hydrazinocarbonyl)-4,5,6,7-tetrahydro-benzo[b]thiophen-2-yl]-benzamide

The title compound 657 was produced in substantially the same manner as in Example 9.

¹H-NMR (CDCl₃, 400 MHz): δ 0.98 (6H, m), 1.87 (7H, m), 2.63 (12H, m), 3.77 (2H, m), 3.84 (3H, s), 6.89 (2H, m), 7.40-8.10 (7H, m)

Mass spectrometric value (ESI-MS) 602 (M−1)

Compound 658 N-[3-(3,4-Dimethyl-benzylidene-hydrazinocarbonyl)-thiophen-2-yl]-3-(3-hydroxy-propylsulfanylmethyl)-benzamide

The title compound 658 was produced in substantially the same manner as in Example 8.

¹H-NMR (CD₃OD, 400 MHz): δ 1.80 (2H, m), 2.30 (3H, s), 2.31 (3H, s), 2.53 (2H, t, J=7.4 Hz), 3.62 (2H, m), 3.85 (2H, s), 7.00 (1H, d, J=6.1 Hz), 7.18 (1H, d, J=7.8 Hz), 7.52 (3H, m), 7.64 (2H, m), 7.90 (1H, s), 7.97 (1H, s), 8.28 (1H, s)

Mass spectrometric value (ESI-MS) 480 (M−1)

Compound 659 3-(3-Hydroxy-propylsulfanylmethyl)-N-[3-(4-methyl-benzylidene-hydrazinocarbonyl)-thiophen-2-yl]-benzamide

The title compound 659 was produced in substantially the same manner as in Example 8.

¹H-NMR (CD₃OD, 400 MHz): δ 1.79 (2H, m), 2.35 (3H, s), 2.53 (2H, t, J=7.3 Hz), 3.62 (2H, t, J=6.2 Hz), 3.82 (2H, s), 6.97 (1H, d, J=5.8 Hz), 7.21 (2H, d, J=7.8 Hz), 7.49 (2H, m), 7.60 (1H, d, J=7.80), 7.69 (2H, d, J=7.8 Hz), 7.87 (1H, m), 7.94 (1H, s), 8.27 (1H, s)

Mass spectrometric value (ESI-MS) 466 (M−1)

Compound 660 N-[3-(4-Fluoro-benzylidene-hydrazinocarbonyl)-thiophen-2-yl]-3-(3-hydroxy-propylsulfanylmethyl)-benzamide

The title compound 660 was produced in substantially the same manner as in Example 8.

¹H-NMR (CD₃OD, 400 MHz): δ 1.80 (2H, m), 2.53 (2H, t, J=7.4 Hz), 3.62 (2H, t, J=6.4 Hz), 3.82 (2H, s), 6.96 (1H, d, J=5.9 Hz), 7.14 (2H, dd, J=8.7 Hz), 7.48 (2H, m), 7.60 (1H, d, J=7.6 Hz), 7.85 (3H, m), 7.93 (1H, s), 8.29 (1H, s)

Mass spectrometric value (ESI-MS) 470 (M−1)

Compound 661 N-[3-(3-Fluoro-benzylidene-hydrazinocarbonyl)-thiophen-2-yl]-3-(3-hydroxy-propylsulfanylmethyl)-benzamide

The title compound 661 was produced in substantially the same manner as in Example 8.

¹H-NMR (CD₃OD, 400 MHz): δ 1.80 (2H, m), 2.54 (2H, t, J=7.3 Hz), 3.62 (2H, t, J=9.4 Hz), 3.86 (2H, s), 7.03 (1H, d, J=5.8 Hz), 7.17 (1H, m), 7.42-7.80 (6H, m), 7.87 (1H, m), 7.98 (1H, bs), 8.35 (1H, s)

Mass spectrometric value (ESI-MS) 470 (M−1)

Compound 662 N-[3-(4-Chloro-3-trifluoromethyl-benzylidene-hydrazinocarbonyl)-thiophen-2-yl]-3-(3-hydroxy-propylsulfanylmethyl)-benzamide

The title compound 662 was produced in substantially the same manner as in Example 8.

¹H-NMR (CD₃OD, 400 MHz): δ 1.80 (1H, m), 2.54 (2H, t, J=7.3 Hz), 3.62 (2H, t, J=6.2 Hz), 3.86 (2H, s), 7.03 (1H, d, J=5.8 Hz), 7.53 (2H, m), 7.66 (2H, m), 7.90 (1H, d, J=7.8 Hz), 7.98 (1H, bs), 8.04 (1H, d, J=8.8 Hz), 8.33 (1H, s), 8.38 (1H, s)

Mass spectrometric value (ESI-MS) 554 (M−1)

Compound 663 3-(3-Hydroxy-propylsulfanylmethyl)-N-[3-(4-methoxy-benzylidene-hydrazinocarbonyl)-thiophen-2-yl]-benzamide

The title compound 663 was produced in substantially the same manner as in Example 8.

¹H-NMR (CD₃OD, 400 MHz): δ 1.80 (2H, m), 2.54 (2H, t, J=7.3 Hz), 3.62 (2H, t, J=6.2 Hz), 3.85 (6H, m), 6.99 (2H, d, J=8.8 Hz), 7.02 (1H, s, J=5.9 Hz), 7.53 (2H, m), 7.65 (1H, d, J=7.8 Hz), 7.79 (2H, d, J=8.5 Hz), 7.90 (1H, d, J=7.8 Hz), 8.30 (1H, s)

Mass spectrometric value (ESI-MS) 482 (M−1)

Compound 664 3-{[(2-Diethylamino-ethyl)-methyl-amino]-methyl}-N-[3-(3,4-dimethyl-benzylidene-hydrazinocarbonyl)-thiophen-2-yl]-benzamide

The title compound 664 was produced in substantially the same manner as in Example 8.

¹H-NMR (CDCl₃, 400 MHz): δ 1.04 (6H, t, J=7.1 Hz), 2.22 (9H, m), 2.62 (8H, m), 3.59 (2H, s), 6.77 (1H, d, J=5.4 Hz), 7.09 (1H, m), 7.44 (5H, m), 7.94 (2H, d, J=7.6 Hz), 8.26 (1H, s)

Mass spectrometric value (ESI-MS) 518 (M−1)

Compound 665 3-{[(2-Diethylamino-ethyl)-methyl-amino]-methyl}-N-[3-(4-methyl-benzylidene-hydrazinocarbonyl)-thiophen-2-yl]-benzamide

The title compound 665 was produced in substantially the same manner as in Example 8.

¹H-NMR (CDCl₃, 400 MHz): δ 1.03 (6H, t, J=7.1 Hz), 2.21 (3H, s), 2.34 (3H, s), 2.59 (8H, m), 3.58 (2H, s), 6.80 (1H, d, J=4.6 Hz), 7.16 (2H, m), 7.42 (2H, m), 7.58 (3H, m), 7.93 (1H, d, J=7.8 Hz), 7.98 (1H, s), 8.28 (1H, s)

Mass spectrometric value (ESI-MS) 504 (M−1)

Compound 666 3-{[(2-Diethylamino-ethyl)-methyl-amino]-methyl}-N-[3-(4-fluoro-benzylidene-hydrazinocarbonyl)-thiophen-2-yl]-benzamide

The title compound 666 was produced in substantially the same manner as in Example 8.

¹H-NMR (CDCl₃, 400 MHz): δ 1.04 (6H, t, J=7.1 Hz), 2.21 (3H, s), 2.62 (8H, m), 3.58 (2H, s), 6.78 (1H, d, J=4.6 Hz), 7.02 (2H, m), 7.42 (2H, m), 7.55 (1H, d, J=7.6 Hz), 7.67 (2H, m), 7.91 (1H, d, J=7.8 Hz), 7.96 (1H, s), 8.36 (1H, s)

Mass spectrometric value (ESI-MS) 508 (M−1)

Compound 667 3{[(2-Diethylamino-ethyl)-methyl-amino]-methyl}-N-[3-(3-fluoro-benzylidene-hydrazinocarbonyl)-thiophen-2-yl]-benzamide

The title compound 667 was produced in substantially the same manner as in Example 8.

¹H-NMR (CDCl₃, 400 MHz): δ 1.04 (6H, t, J=7.1 Hz), 2.20 (3H, s), 2.60 (8H, m), 3.57 (2H, s), 6.76 (1H, bs), 7.02 (1H, m), 7.41 (6H, m), 7.91 (1H, d, J=7.8 Hz), 7.97 (1H, s), 8.38 (1H, bs)

Mass spectrometric value (ESI-MS) 508 (M−1)

Compound 668 N-[3-(4-Chloro-3-trifluoromethyl-benzylidene-hydrazinocarbonyl)-thiophen-2-yl]-3-{[(2-diethylamino-ethyl)-methyl-amino]-methyl}-benzamide

The title compound 668 was produced in substantially the same manner as in Example 8.

¹H-NMR (CDCl₃, 400 MHz): δ 1.02 (6H, t, J=7.1 Hz), 2.20 (3H, s), 2.58 (8H, m), 3.56 (2H, s), 6.74 (1H, bs), 7.41 (2H, m), 7.54 (2H, d, J=7.6 Hz), 7.76 (1H, dd, J=8.3 Hz, J=1.4 Hz), 7.88 (2H, m), 7.96 (1H, s), 8.45 (1H, bs)

Mass spectrometric value (ESI-MS) 592 (M−1)

Compound 669 3-{[(2-Diethylamino-ethyl)-methyl-amino]-methyl}-N-[3-(4-methoxy-benzylidene-hydrazinocarbonyl)-thiophen-2-yl]-benzamide

The title compound 669 was produced in substantially the same manner as in Example 8.

¹H-NMR (CDCl₃, 400 MHz): δ 1.01 (6H, t, J=7.1 Hz), 2.19 (3H, s), 2.56 (8H, m), 3.56 (2H, s), 3.75 (3H, s), 6.75 (1H, m), 6.81 (2H, m), 7.42 (2H, m), 7.87 (3H, m), 7.90 (1H, d, J=7.84), 7.97 (1H, s), 8.32 (1H, s)

Mass spectrometric value (ESI-MS) 520 (M−1)

Compound 670 3-{[Bis-(2-hydroxy-propyl)-amino]-methyl}-N-[3-(3,4-dimethyl-benzylidene-hydrazinocarbonyl)-thiophen-2-yl]-benzamide

The title compound 670 was produced in substantially the same manner as in Example 8.

¹H-NMR (CD₃OD, 400 MHz): δ 1.11 (6H, m), 2.30 (3H, s), 2.32 (3H, s), 2.52 (4H, m), 3.83 (4H, m), 7.01 (1H, d, J=5.8 Hz), 7.19 (1H, d, J=7.8 Hz), 7.53 (3H, m), 7.67 (2H, m), 7.93 (1H, d, J=7.6 Hz), 8.06 (1H, m), 8.29 (1H, s)

Mass spectrometric value (ESI-MS) 521 (M−1)

Compound 671 3-{[Bis-(2-hydroxy-propyl)-amino]-methyl}-N-[3-(4-methyl-benzylidene-hydrazinocarbonyl)-thiophen-2-yl]-benzamide

The title compound 671 was produced in substantially the same manner as in Example 8.

¹H-NMR (CD₃OD, 400 MHz): δ 1.11 (6H, d, J=6.1 Hz), 2.39 (3H, s), 2.52 (4H, m), 3.82 (4H, m), 7.01 (1H, m), 7.26 (2H, d, J=7.6 Hz), 7.53 (2H, m), 7.68 (1H, d, J=7.1 Hz), 7.74 (2H, d, J=7.8 Hz), 7.92 (1H, d, J=7.6 Hz), 8.06 (1H, m), 8.33 (1H, s)

Mass spectrometric value (ESI-MS) 507 (M−1)

Compound 672 3-{[Bis-(2-hydroxy-propyl)-amino]-methyl}-N-[3-(4-fluoro-benzylidene-hydrazinocarbonyl)-thiophen-2-yl]-benzamide

The title compound 672 was produced in substantially the same manner as in Example 8.

¹H-NMR (CD₃OD, 400 MHz): δ 1.10 (6H, d, J=6.3 Hz), 2.51 (4H, m), 3.86 (4H, m), 7.02 (1H, d, J=5.9 Hz), 7.18 (2H, dd, J=8.4 Hz, J=8.4 Hz), 7.53 (2H, m), 7.68 (1H, dd, J=7.6 Hz), 7.91 (3H, m), 8.06 (1H, m), 8.35 (1H, s)

Mass spectrometric value (ESI-MS) 511 (M−1)

Compound 673 3-{[Bis-(2-hydroxy-propyl)-amino]-methyl}-N-[3-(3-fluoro-benzylidene-hydrazinocarbonyl)-thiophen-2-yl]-benzamide

The title compound 673 was produced in substantially the same manner as in Example 8.

¹H-NMR (CD₃OD, 400 MHz): δ 1.11 (6H, m), 2.52 (4H, m), 3.87 (4H, m), 7.03 (1H, d, J=6.1 Hz), 7.15 (1H, m), 7.40-7.75 (6H, m), 7.90 (1H, m), 8.07 (1H, m), 8.36 (1H, m)

Mass spectrometric value (ESI-MS) 511 (M−1)

Compound 674 3-[(4-Chloro-3-trifluoromethyl-benzylidene)-amino]-2-(3-{[(2-diethylamino-ethyl)-methyl-amino]-methyl}-phenyl)-5,6,7,8-tetrahydro-3H-benzo[4,5]thieno[2,3-d]pyrimidin-4-one

The title compound 674 was produced in substantially the same manner as in Example 8.

¹H-NMR (CDCl₃, 400 MHz): δ 0.99 (6H, t, J=7.1 Hz), 1.90 (4H, m), 2.12 (3H, s), 2.50 (8H, m), 2.82 (2H, m), 3.05 (2H, m), 3.52 (2H, s), 7.38 (2H, m), 7.54 (2H, m), 7.62 (1H, bs), 7.78 (1H, m), 7.98 (1H, m), 9.18 (1H, s)

Mass spectrometric value (ESI-MS) 630 (M+1)

Compound 675 2-(3-{[(2-Diethylamino-ethyl)-methyl-amino]-methyl}-phenyl)-3-[(4-methoxy-benzylidene-)-amino]-5,6,7,8-tetrahydro-3H-benzo[4,5]thieno[2,3-d]pyrimidin-4-one

The title compound 675 was produced in substantially the same manner as in Example 8.

¹H-NMR (CDCl₃, 400 MHz): δ 1.00 (6H, t, J=7.1 Hz), 1.89 (4H, m), 2.11 (3H, s), 2.52 (8H, m), 2.81 (2H, m), 3.06 (2H, m), 3.50 (2H, s), 3.84 (3H, s), 6.89 (2H, d, J=8.8 Hz), 7.35 (2H, m), 7.58 (1H, m), 7.66 (3H, m), 8.77 (1H, s)

Mass spectrometric value (ESI-MS) 558 (M+1)

Compound 676 N-[4-Bromo-2-(4-methyl-benzylidene-hydrazinocarbonyl)-phenyl]-3-(2-hydroxy-ethanesulfonylmethyl)-benzamide

The title compound 676 was produced in the same manner as in Example 6.

¹H-NMR (CD₃OD, 400 MHz): δ 8.58 (1H, d, J=8.8 Hz), 8.34 (1H, s), 8.07 (1H, d, J=2.2 Hz), 8.00 (2H, s), 7.23-7.78 (3H, m), 7.57-7.63 (2H, m), 7.27 (2H, d, J=2.0 Hz), 4.39 (1H, d, J=13.2 Hz), 4.20 (1H, d, J=13.2 Hz), 3.96-4.05 (2H, m), 3.00-3.15 (1H, m), 2.80-2.95 (1H, m), 2.39 (3H, s)

Mass spectrometric value (ESI-MS) 556, 558 (M−1)

Compound 677 N-[4-Bromo-2-(4-methyl-benzylidene-hydrazinocarbonyl)-phenyl]-3-(2-hydroxy-ethanesulfinylmethyl)-benzamide

The title compound 677 was produced in the same manner as in Example 6.

¹H-NMR (CD₃OD, 400 MHz): δ 8.61 (1H, d, J=9.0 Hz), 8.34 (1H, s), 8.06-8.13 (2H, m), 8.04 (1H, d, J=8.3 Hz), 7.72-7.79 (4H, m), 7.60 (1H, dd, J=7.8 Hz, J=7.8 Hz), 7.28 (2H, d, J=8.1 Hz), 4.83 (2H, s), 4.05 (2H, t, J=5.6 Hz), 3.20 (2H, t, J=5.6 Hz), 2.39 (3H, s)

Mass spectrometric value (ESI-MS) 542, 543 (M−1)

Compound 678 N-[4-Bromo-2-(4-chloro-3-trifluoromethyl-benzylidene-hydrazinocarbonyl)-phenyl]-3-(2-hydroxy-ethanesulfonylmethyl)-benzamide

The title compound 678 was produced in the same manner as in Example 6.

¹H-NMR (CD₃OD, 400 MHz): δ 8.55 (1H, d, J=9.0 Hz), 8.40 (1H, s), 8.32 (1H, s), 8.07 (1H, d, J=2.0 Hz), 8.05 (1H, s, J=8.5 Hz), 7.96-8.05 (2H, m), 7.77 (1H, dd, J=2.0 Hz, J=8.8 Hz), 7.69 (1H, d, J=8.3 Hz), 7.56-7.66 (2H, m), 4.39 (1H, d, J=12.9 Hz), 4.20 (1H, d, J=13.2 Hz), 3.96-4.03 (2H, m), 3.03-3.13 (1H, m), 2.87 (1H, dt, J=4.2 Hz, J=13.4 Hz)

Mass spectrometric value (ESI-MS) 664, 646 (M−1)

Compound 679 N-[4-Bromo-2-(4-chloro-3-trifluoromethyl-benzylidene-hydrazinocarbonyl)-phenyl]-3-(2-hydroxy-ethanesulfinylmethyl)-benzamide

The title compound 679 was produced in the same manner as in Example 6.

¹H-NMR (CDCl₃, 400 MHz): δ 8.70-8.80 (1H, m), 8.20-8.27 (1H, m), 8.05-8.15 (2H, m), 7.97 (2H, s), 7.60-7.70 (3H, m), 7.49-7.60 (2H, m), 4.52 (2H, m), 4.22-4.26 (2H, m), 3.10-3.15 (2H, m)

Mass spectrometric value (ESI-MS) 628, 630 (M−1)

Compound 680 N-[4-Chloro-2-(3-fluoro-benzylidene-hydrazinocarbonyl)-phenyl]-3-(furan-2-ylmethylsulfanylmethyl)-benzamide

The title compound 680 was produced in the same manner as in Example 5.

¹H-NMR (CD₃OD, 400 MHz): δ 8.64 (1H, d, J=9.0 Hz), 8.36 (1H, s), 7.93-7.97 (2H, m), 7.85-7.90 (1H, m), 7.69 (1H, d, J=10.0 Hz), 7.63 (1H, dd, J=2.4 Hz, J=9.0 Hz), 7.58 (2H, dd, J=7.6 Hz, J=7.6 Hz), 7.50 (1H, dd, J=7.6 Hz, J=7.6 Hz), 7.40-7.48 (2H, m), 7.18 (2H, m), 6.29-6.33 (1H, m), 6.21 (1H, d, J=3.2 Hz), 3.81 (2H, s), 3.64 (2H, s)

Mass spectrometric value (ESI-MS) 520, 522 (M−1)

Compound 681 N-[4-Chloro-2-(4-fluoro-benzylidene-hydrazinocarbonyl)-phenyl]-3-(furan-2-ylmethylsulfanylmethyl)-benzamide

The title compound 681 was produced in the same manner as in Example 5.

¹H-NMR (CD₃OD, 400 MHz): δ 8.64 (1H, d, J=9.0 Hz), 8.35 (1H, s), 7.85-7.96 (5H, m), 7.62 (1H, dd, J=2.4 Hz, J=9.0 Hz), 7.57 (1H, d, J=7.8 Hz), 7.50 (1H, dd, J=7.7 Hz, J=7.7 Hz), 7.40-7.42 (1H, m), 7.18 (2H, dd, J=8.8 Hz, J=8.8 Hz), 7.31 (1H, dd, J=2.0 Hz, J=3.2 Hz), 6.21 (1H, d, J=3.2 Hz), 3.81 (2H, s), 3.64 (2H, s)

Mass spectrometric value (ESI-MS) 520, 522 (M−1)

Compound 682 N-[4-Chloro-2-(4-methyl-benzylidene-hydrazinocarbonyl)-phenyl]-3-(furan-2-ylmethylsulfanylmethyl)-benzamide

The title compound 682 was produced in the same manner as in Example 5.

¹H-NMR (CD₃OD, 400 MHz): δ 8.65 (1H, d, J=9.0 Hz), 8.33 (1H, s), 7.91-7.96 (2H, m), 7.85-7.90 (1H, m), 7.73 (2H, d, J=8.0 Hz), 7.62 (1H, dd, J=2.4 Hz, J=9.0 Hz), 7.58 (1H, d, J=7.6 Hz), 7.50 (1H, dd, J=7.8 Hz, J=7.8 Hz), 7.40-7.42 (1H, m), 7.26 (2H, d, J=8.1 Hz), 6.29-6.33 (1H, m), 6.20-6.23 (1H, m), 3.82 (2H, s), 3.64 (2H, s), 2.38 (3H, s)

Mass spectrometric value (ESI-MS) 516, 518 (M−1)

Compound 683 N-[4-Chloro-2-(3,4-dimethyl-benzylidene-hydrazinocarbonyl)-phenyl]-3-(furan-2-ylmethylsulfanylmethyl)-benzamide

The title compound 683 was produced in the same manner as in Example 5.

¹H-NMR (CD₃OD, 400 MHz): δ 8.66 (1H, d, J=8.8 Hz), 8.30 (1H, s), 7.86-7.98 (3H, m), 7.48-7.78 (5H, m), 7.41 (1H, s), 7.15-7.27 (1H, m), 6.29-6.35 (1H, m), 6.20-6.25 (1H, m), 3.82 (2H, s), 3.64 (2H, s), 2.31 (6H, s)

Mass spectrometric value (ESI-MS) 530, 532 (M−1)

Compound 684 N1-[4-Chloro-2-({2-[(E)-1-(3,4-dimethylphenyl)methylidene]hydrazino}carbonyl}phenyl}-3-{[{3-[(3-{[4-chloro-2-({2-[(E)-1-(3,4-dimethylphenyl)methylidene]hydrazino}carbonyl}anilino}carbonyl}benzyl}(methyl)amino)propyl](methyl)amino)methyl)benzamide

The title compound 684 was produced in the same manner as in Example 8.

¹H-NMR (CDCl₃, 400 MHz): δ 11.57 (2H, s), 10.57 (2H, s), 8.67 (2H, d, J=9.0 Hz), 8.44 (2H, s), 7.80 (2H, s), 7.71-7.73 (2H, m), 7.64 (2H, s), 7.56 (2H, s), 7.38 (4H, dd, J=7.8 Hz, J=7.8 Hz), 7.20-7.35 (4H, m), 7.10 (2H, d, J=7.8 Hz), 3.53 (4H, s), 2.46 (4H, s), 2.23 (6H, s), 2.18 (6H, s), 2.14 (6H, s), 1.80 (2H, s), 1.61 (4H, s)

Mass spectrometric value (ESI-MS) 935 (M−1)

Compound 685 N1-[4-Chloro-2-({2-[(E)-1-(3-fluorophenyl)methylidene]hydrazino}carbonyl}phenyl}-3-{[{3-[(3-{[4-chloro-2-({2-[(E)-1-(3-fluorophenyl)methylidene]hydrazino}carbonyl}-anilino}carbonyl}benzyl}(methyl)amino)propyl)(methyl)amino]methyl}-benzamide

The title compound 685 was produced in the same manner as in Example 8.

¹H-NMR (CD₃OD, 400 MHz): δ 8.59 (2H, d, J=9.0 Hz), 8.40 (2H, s), 7.88-7.90 (4H, m), 7.85 (2H, s), 7.79 (2H, d, J=7.1 Hz), 7.63 (2H, d, J=10.5 Hz), 7.52-7.58 (4H, m), 7.35-7.45 (6H, m), 7.12-7.20 (2H, m), 3.62 (4H, s), 2.53 (4H, m), 2.23 (6H, s), 1.78-1.85 (2H, m)

Mass spectrometric value (ESI-MS) 915 (M−1)

Compound 686 N-[4-Chloro-2-(3,4-dimethyl-benzylidene-hydrazinocarbonyl)-phenyl]-3-(furan-2-ylmethanesulfonylmethyl)-benzamide

The title compound 686 was produced in the same manner as in Example 6.

¹H-NMR (CDCl₃, 400 MHz): δ 8.64 (1H, d, J=9.0 Hz), 8.30 (1H, s), 8.01 (2H, s), 7.88-7.94 (2H, m), 7.52-7.68 (5H, m), 7.20 (1H, d, J=7.8 Hz), 6.50 (1H, d, J=3.2 Hz), 6.42-6.45 (1H, m), 4.25-4.37 (2H, m), 4.11 (1H, d, J=4.7 Hz), 4.08 (1H, d, J=4.7 Hz), 2.32 (3H, s), 2.31 (3H, s)

Mass spectrometric value (ESI-MS) 562, 564 (M−1)

Compound 687 N-[4-Chloro-2-(3,4-dimethyl-benzylidene-hydrazinocarbonyl)-phenyl]-3-(furan-2-ylmethanesulfinylmethyl)-benzamide

The title compound 687 was produced in the same manner as in Example 6.

¹H-NMR (CDCl₃, 400 MHz): δ 6.37 (1H, s), 8.72 (1H, d, J=8.0 Hz), 8.00-8.22 (3H, m), 7.40-7.80 (7H, m), 6.54 (1H, d, J=3.4 Hz), 6.40-6.45 (1H, m), 4.29 (2H, s), 4.20 (2H, s), 2.29 (6H, s)

Mass spectrometric value (ESI-MS) 546, 548 (M−1)

Compound 688 N-[4-Chloro-2-(4-chloro-3-trifluoromethyl-benzylidene-hydrazinocarbonyl)-phenyl]-3-(furan-2-ylmethanesulfonylmethyl)-benzamide

The title compound 688 was produced in the same manner as in Example 6.

¹H-NMR (CDCl₃, 400 MHz): δ 8.60 (1H, d, J=9.0 Hz), 8.39 (1H, s), 8.32 (1H, s), 7.89-8.07 (4H, m), 7.55-7.73 (5H, m), 6.49 (1H, m), 6.41-6.46 (1H, m), 4.31 (2H, dd, J=13.4 Hz, J=15.8 Hz), 4.09 (2H, dd, J=10.0 Hz, J=14.2 Hz)

Mass spectrometric value (ESI-MS) 636, 638 (M−1)

Compound 689 N-[4-Chloro-2-(4-chloro-3-trifluoromethyl-benzylidene-hydrazinocarbonyl)-phenyl]-3-(furan-2-ylmethanesulfinylmethyl)-benzamide

The title compound 689 was produced in the same manner as in Example 6.

¹H-NMR (CDCl₃, 400 MHz): δ 8.60 (1H, d, J=9.3 Hz), 8.39 (1H, s), 8.32 (1H, s), 7.98-8.09 (3H, m), 7.94 (1H, d, J=2.2 Hz), 7.69 (2H, d, J=8.0 Hz), 7.56-7.67 (3H, m), 6.55 (1H, d, J=3.2 Hz), 6.40-6.47 (1H, m), 4.54 (2H, s), 4.51 (2H, s)

Mass spectrometric value (ESI-MS) 620 (M−1)

Compound 690 N1-[4-Chloro-2-({2-[(E)-1-(4-chloro-3-trifluoromethyl-phenyl)methylidene]hydrazino}carbonyl)phenyl)-3-{[{6-[(3-{[4-chloro-2-({2-[(E)-1-(4-chloro-3-trifluoromethyl-phenyl)methylidene]hydrazino}-carbonyl}anilino}carbonyl}benzyl}(methyl)amino)hexyl)(methyl)amino]-methyl]benzamide

The title compound 690 was produced in the same manner as in Example 8.

Mass spectrometric value (ESI-MS) 1125, 1127 (M−1)

Compound 691 2-{3-[4-Chloro-2-(3-fluoro-benzylidene-hydrazinocarbonyl)-phenylcarbamoyl]-benzylsulfanyl}-ethanesulfonic acid

The title compound 691 was produced in the same manner as in Example 11.

¹H-NMR (CD₃OD, 400 MHz): δ 8.53 (1H, d, J=9.0 Hz), 8.34 (1H, s), 7.40-8.00 (10H, m), 4.84 (2H, s), 2.90-3.10 (2H, m), 2.70-2.86 (2H, m)

Mass spectrometric value (ESI-MS) 548 (M−1)

Compound 692 2-{3-[4-Chloro-2-(3-methyl-benzylidene-hydrazinocarbonyl)-phenylcarbamoyl]-benzylsulfanyl}-ethanesulfonic acid

The title compound 692 was produced in the same manner as in Example 11.

¹H-NMR (CD₃OD, 400 MHz): δ 8.56 (1H, d, J=8.8 Hz), 7.20-8.35 (11H, m), 3.84-3.90 (2H, m), 2.92-3.04 (2H, m), 2.70-2.88 (2H, m), 2.30-2.40 (3H, m)

Mass spectrometric value (ESI-MS) 544 (M−1)

Compound 693 2-{3-[4-Chloro-2-(4-methyl-benzylidene-hydrazinocarbonyl)-phenylcarbamoyl]-benzylsulfanyl}-ethanesulfonic acid

The title compound 693 was produced in the same manner as in Example 11.

¹H-NMR (CD₃OD, 400 MHz): δ 8.55 (1H, d, J=8.8 Hz), 8.32 (1H, s), 7.10-8.00 (10H, m), 3.88 (2H, s), 2.90-3.10 (2H, m), 2.68-2.86 (2H, m), 2.38 (3H, s)

Mass spectrometric value (ESI-MS) 544 (M−1)

Compound 694 2-{3-[4-Chloro-2-(3,4-dimethyl-benzylidene-hydrazinocarbonyl)-phenylcarbamoyl]-benzylsulfanyl}-ethanesulfonic acid

The title compound 694 was produced in the same manner as in Example 11.

¹H-NMR (CD₃OD, 400 MHz): δ 8.56 (1H, d, J=9.0 Hz), 8.29 (1H, s), 7.46-8.00 (8H, m), 7.18-7.25 (1H, m), 3.87 (2H, s), 2.94-3.10 (2H, m), 2.75-2.86 (2H, m), 2.25-2.35 (6H, m)

Mass spectrometric value (ESI-MS) 582 (M+23)

Compound 695 6-Bromo-3-[(4-fluoro-benzylidene-)-amino]-2-[3-(2-hydroxy-ethylsulfanylmethyl)-phenyl]-3H-quinazolin-4-one

The title compound 695 was produced in the same manner as in Example 10.

¹H-NMR (CDCl₃, 400 MHz): δ 8.98-9.00 (1H, m), 8.46 (1H, s), 7.85 (1H, dd, J=2.2 Hz, J=8.5 Hz), 7.65-7.72 (3H, m), 7.58 (1H, dd, J=1.7 Hz, J=7.3 Hz), 7.35-7.43 (2H, m), 7.07-7.13 (3H, m), 3.73 (2H, s), 3.56-3.64 (2H, m), 2.52-2.58 (2H, m)

Mass spectrometric value (ESI-MS) 534, 536, 537 (M+23)

Compound 696 6-Bromo-2-[3-(2-hydroxy-ethylsulfanylmethyl)-phenyl]-3-[(4-methyl-benzylidene-)-amino]-3H-quinazolin-4-one

The title compound 696 was produced in the same manner as in Example 10.

¹H-NMR (CDCl₃, 400 MHz): δ 8.85 (1H, s), 8.41 (1H, d, J=2.2 Hz), 7.91 (1H, d, J=8.0 Hz), 7.79 (1H, dd, J=2.4 Hz, J=8.8 Hz), 7.59-7.64 (2H, m), 7.52-7.56 (3H, m), 7.28-7.36 (2H, m), 7.14-7.20 (1H, m), 3.67 (2H, s), 3.49 (2H, t, J=6.0 Hz), 2.46 (2H, t, J=6.0 Hz), 2.36 (1H, s), 2.33 (3H, s)

Mass spectrometric value (ESI-MS) 530, 532, 533 (M+23)

Compound 697 6-Bromo-3-[(3,4-dimethyl-benzylidene-)-amino]-2-[3-(2-hydroxy-ethylsulfanylmethyl)-phenyl]-3H-quinazolin-4-one

The title compound 697 was produced in the same manner as in Example 10.

¹H-NMR (CDCl₃, 400 MHz): δ 8.78 (1H, s), 8.41 (2H, d, J=2.2 Hz), 7.79 (1H, dd, J=2.4 Hz, J=8.8 Hz), 7.64 (1H, s), 7.60 (1H, d, J=8.8 Hz), 7.53-7.57 (1H, m), 7.42 (1H, s), 7.28-7.38 (3H, m), 7.11 (1H, d, J=7.8 Hz), 3.67 (2H, s), 3.49 (2H, t, J=6.0 Hz), 2.46 (2H, t, J=6.0 Hz), 2.24 (3H, s), 2.22-2.27 (1H, m), 2.20 (3H, s)

Mass spectrometric value (ESI-MS) 546, 547 (M+23)

Compound 698 6-Bromo-3-[(4-chloro-3-trifluoromethyl-benzylidene-)-amino]-2-[3-(2-hydroxy-ethylsulfanylmethyl)-phenyl]-3H-quinazolin-4-one

The title compound 698 was produced in the same manner as in Example 10.

¹H-NMR (CDCl₃, 400 MHz): δ 9.27 (1H, s), 8.46 (1H, d, J=2.2 Hz), 7.94 (1H, s), 7.86 (1H, dd, J=2.2 Hz, J=8.5 Hz), 7.75 (1H, d, J=8.3 Hz), 7.65-7.68 (2H, m), 7.54 (2H, d, J=7.8 Hz), 7.32-7.45 (2H, m), 3.75 (2H, s), 3.61 (2H, dt, J=5.9 Hz, J=5.9 Hz), 2.57 (2H, t, J=6.0 Hz), 2.03 (1H, t, J=6.1 Hz)

Mass spectrometric value (ESI-MS) 620 (M+23)

Compound 699 N-[4-Chloro-2-(3-methyl-benzylidene-hydrazinocarbonyl)-phenyl]-3-(furan-2-ylmethylsulfanylmethyl)-benzamide

The title compound 699 was produced in the same manner as in Example 5.

¹H-NMR (CD₃OD, 400 MHz): δ 8.65 (1H, d, J=9.0 Hz), 8.34 (1H, s), 7.91-7.96 (2H, m), 7.85-7.90 (1H, m), 7.69 (1H, s), 7.61 (2H, dd, J=2.4 Hz, J=9.0 Hz), 7.57 (1H, d, J=7.8 Hz), 7.49 (1H, dd, J=7.6 Hz, J=7.6 Hz), 7.41 (1H, dd, J=0.8 Hz, J=2.0 Hz), 7.24-7.34 (2H, m), 6.30 (1H, dd, J=2.0 Hz, J=3.2 Hz), 6.21 (1H, d, J=3.2 Hz), 3.81 (2H, s), 3.63 (2H, s), 2.38 (3H, s)

Mass spectrometric value (ESI-MS) 516, 518 (M−1)

Compound 700 N-[4-Chloro-2-(4-chloro-3-trifluoromethyl-benzylidene-hydrazinocarbonyl)-phenyl]-3-(furan-2-ylmethylsulfanylmethyl)-benzamide

The title compound 700 was produced in the same manner as in Example 5.

¹H-NMR (CD₃OD, 400 MHz): δ 8.62 (1H, d, J=9.0 Hz), 8.39 (1H, s), 8.31 (1H, s), 8.04 (1H, d, J=6.8 Hz), 7.92-7.96 (2H, m), 7.87 (1H, d, J=7.8 Hz), 7.69 (1H, d, J=8.6 Hz), 7.64 (1H, dd, J=2.4 Hz, J=9.0 Hz), 7.57 (1H, d, 7.6 Hz), 7.50 (1H, dd, J=7.7 Hz, J=7.7 Hz), 7.40 (1H, dd, J=0.8 Hz, J=2.0 Hz), 6.28-6.33 (1H, m), 6.21 (1H, d, J=7.3 Hz), 3.81 (2H, s), 3.64 (2H, s)

Mass spectrometric value (ESI-MS) 604, 606 (M−1)

Compound 701 N1-[4-Chloro-2-({2-[(E)-1-(4-fluorophenyl)methylidene]-hydrazino}carbonyl}phenyl}-3-{[{3-[(3-{[4-chloro-2-({2-[(E)-1-(4-fluorophenyl)methylidene]hydrazino}carbonyl}anilino}carbonyl}benzyl}-(methyl)amino)propyl)(methyl)amino]methyl]benzamide

The title compound 701 was produced in the same manner as in Example 8.

¹H-NMR (CD₃OD, 400 MHz): δ 8.59 (2H, d, J=8.8 Hz), 8.41 (2H, s), 7.82-7.90 (8H, m), 7.79 (2H, d, J=7.1 Hz), 7.53 (2H, dd, J=2.4 Hz, J=9.0 Hz), 7.35-7.45 (4H, m), 7.14 (4H, dd, J=8.8 Hz, J=8.8 Hz), 3.59 (4H, s), 2.49 (4H, t, J=6.8 Hz), 2.20 (6H, s), 1.75-1.85 (2H, m)

Mass spectrometric value (ESI-MS) 915, 917 (M−1)

Compound 702 N1-[4-Chloro-2-({2-[(E)-1-(4-methylphenyl)methylidene]-hydrazino}carbonyl}phenyl}-3-{[{3-[(3-{[4-chloro-2-({2-[(E)-1-(4-methylphenyl)methylidene]hydrazino}carbonyl}anilino}carbonyl}benzyl}(methyl)amino)propyl)(methyl)amino]methyl]benzamide

The title compound 702 was produced in the same manner as in Example 8.

¹H-NMR (CDCl₃, 400 MHz): δ 8.66 (2H, d, J=9.0 Hz), 8.46 (2H, s), 7.72-7.82 (4H, m), 7.58-7.68 (6H, m), 7.25-7.40 (4H, m), 7.12-7.16 (6H, m), 3.53 (4H, bs), 2.46 (4H, bs), 2.15 (6H, bs), 1.81 (2H, bs)

Mass spectrometric value (ESI-MS) 907, 909 (M−1)

Example 10 Compound 703 2-(3-{6-Chloro-3-[(4-chloro-3-trifluoromethyl-benzylidene)-amino]-4-oxo-3,4-dihydro-quinazolin-2-yl}-benzylsulfanyl)-ethanesulfonic acid

Methyl 2-amino-5-chlorobenzoate (compound A) (4.0 g) was dissolved in anhydrous methylene chloride (80.0 ml). Subsequently, pyridine (2.8 ml) and 3-(chloromethyl)benzoyl chloride (compound B) (5.0 g) were added to the solution at room temperature, and the mixture was stirred at that temperature for 2 hr. After the completion of the reaction, distilled water was added thereto, and the mixture was subjected to separatory extraction with chloroform. The organic layer was washed with a saturated aqueous sodium chloride solution and saturated brine, was dried over sodium sulfate, and was then concentrated to give methyl 5-chloro-2-[3-(chloromethyl)benzoyl]aminobenzoate as a useful intermediate (3.32 g, yield 100%).

Subsequently, methyl 5-chloro-2-[3-(chloromethyl)benzoyl]-aminobenzoate (1.8 g) was dissolved in anhydrous methylene chloride. Triethylamine (1.5 ml) and 2-mercaptoethanesulfonic acid sodium salt (compound B′) (1.3 g) were added to the solution at room temperature, and the mixture was stirred at 40° C. for 4 days. After the completion of the reaction, distilled water was added thereto at room temperature, and the mixture was subjected to separatory extraction with chloroform. The organic layer was washed with a saturated aqueous sodium chloride solution, was dried over sodium sulfate, and was then concentrated. The residue was purified by column chromatography on silica gel to give 5-chloro-2-[3-(2-sulfo-ethylsulfanylmethyl)-benzoylamino]-benzoic acid methyl ester as a useful intermediate (1.08 g, yield 46.1%).

5-Chloro-2-[3-(2-sulfo-ethylsulfanylmethyl)-benzoylamino]-benzoic acid methyl ester (1.08 g) produced by the above reaction was dissolved in ethanol (11.0 ml). Hydrazine monohydrate (1.0 ml) was added to the solution at room temperature, and the mixture was heated under reflux with stirring for 3 days. After the completion of the reaction, the reaction solution was allowed to cool at room temperature. The reaction solution as such was then concentrated, and the residue was purified by column chromatography on silica gel to give 2-[3-(3-amino-6-chloro-4-oxo-3,4-dihydroquinazolin-2-yl)-benzylsulfanyl]-ethanesulfonic acid as a quinazolone compound (542 mg, yield 52.1%).

2-[3-(3-Amino-6-chloro-4-oxo-3,4-dihydroquinazolin-2-yl)-benzylsulfanyl]-ethanesulfonic acid (50.0 mg) was dissolved in anhydrous toluene (1.0 ml). Subsequently, 4-chloro-3-trifluoromethylbenzaldehyde (compound C) (50.0 μl) was added to the solution at room temperature, and the mixture was heated under reflux with stirring for 12 hr. After the completion of the reaction, the reaction solution was allowed to cool at room temperature, distilled water was added thereto, and the mixture was subjected to separatory extraction with chloroform. The organic layer was washed with a saturated aqueous sodium chloride solution and saturated brine, was dried over sodium sulfate, and was then concentrated. The residue was purified by column chromatography on silica gel, followed by drying through a vacuum pump to give the title compound 703 (32.0 mg, yield 44.0%).

¹H-NMR (CDCl₃, 400 MHz): δ 9.16 (1H, s), 8.15-8.25 (1H, m), 7.38-7.90 (9H, m), 3.84 (2H, s), 2.97-3.05 (2H, m), 2.80-2.87 (2H, m)

Mass spectrometric value (ESI-MS) 614, 616 (M−1)

Compound 704 N1-[4-Chloro-2-({2-[(E)-1-(3-fluorophenyl)methylidene]hydrazino}carbonyl}phenyl}-3-{[{6-[(3-{[4-chloro-2-({2-[(E)-1-(3-fluorophenyl)methylidene]hydrazino}carbonyl}-anilino}carbonyl}benzyl}(methyl)amino)hexyl)(methyl)amino]methyl]-benzamide

The title compound 704 was produced in the same manner as in Example 8.

¹H-NMR (CDCl₃, 400 MHz): δ 8.60 (2H, d, J=9.0 Hz), 8.35 (2H, s), 7.88-7.95 (4H, m), 7.30-7.80 (14H, m), 7.10-7.20 (2H, m), 3.69 (4H, s), 2.47 (4H, t, J=7.3 Hz), 2.27 (6H, s), 1.50-1.60 (4H, m), 1.25-1.37 (4H, m)

Mass spectrometric value (ESI-MS) 957 (M−1)

Compound 705 N1-[4-Chloro-2-({2-[(E)-1-(3-methylphenyl)methylidene]hydrazino}carbonyl}phenyl}-3-{[{6-[(3-{[4-chloro-2-({2-[(E)-1-(3-methylphenyl)methylidene]hydrazino}carbonyl}-anilino}carbonyl}benzyl}(methyl)amino)hexyl)(methyl)amino]methyl]-benzamide

The title compound 705 was produced in the same manner as in Example 8.

¹H-NMR (CDCl₃, 400 MHz): δ 8.61 (2H, d, J=8.8 Hz), 8.35 (2H, s), 7.85-7.93 (4H, s), 7.63 (2H, s), 7.45-7.57 (10H, m), 7.14-7.30 (4H, m), 3.58 (4H, s), 2.35-2.45 (4H, m), 2.34 (6H, s), 2.18 (6H, s), 1.53 (4H, bs), 1.32 (4H, bs)

Mass spectrometric value (ESI-MS) 949 (M−1)

Compound 706 N1-[4-Chloro-2-({2-[(E)-1-(4-methylphenyl)methylidene]hydrazino}carbonyl}phenyl}-3-{[{6-[(3-{[4-chloro-2-({2-[(E)-1-(4-methylphenyl)methylidene]hydrazino}carbonyl}-anilino}carbonyl}benzyl}(methyl)amino)hexyl)(methyl)amino]methyl]-benzamide

The title compound 706 was produced in the same manner as in Example 8.

¹H-NMR (CDCl₃, 400 MHz): δ 8.60 (2H, d, J=8.8 Hz), 8.34 (2H, s), 7.83-7.98 (8H, m), 7.66 (2H, d, J=7.8 Hz), 7.48-7.60 (4H, m), 7.21 (6H, d, J=7.8 Hz), 3.78 (4H, s), 2.55-2.60 (4H, m), 2.30-2.35 (12H, m), 1.59 (4H, bs), 1.35 (4H, bs)

Mass spectrometric value (ESI-MS) 949 (M−1)

Compound 707 3-{[Bis-(2-hydroxy-propyl)-amino]-methyl}-N-[2-(4-chloro-3-trifluoromethyl-benzylidene-hydrazinocarbonyl)-4-methyl-thiophen-3-yl]-benzamide

The title compound 707 was produced in the same manner as in Example 8.

Mass spectrometric value (ESI-MS) 609, 611, 612 (M−1)

Compound 708 2-{3-[4-Chloro-2-(4-fluoro-benzylidene-hydrazinocarbonyl)-phenylcarbamoyl]-benzylsulfanyl}-ethanesulfonic acid

The title compound 708 was produced in the same manner as in Example 11.

¹H-NMR (CD₃OD, 400 MHz): δ 8.54 (1H, d, J=8.8 Hz), 8.34 (1H, s), 7.98 (1H, s), 7.35-7.92 (7H, m), 7.14-7.22 (2H, m), 3.88 (2H, s), 2.95-3.06 (2H, m), 2.70-2.86 (2H, m)

Mass spectrometric value (ESI-MS) 548 (M−1)

Example 11 Compound 709 2-{3-[4-Chloro-2-(4-chloro-3-trifluoromethyl-benzylidene-hydrazinocarbonyl)-phenylcarbamoyl]-benzylsulfanyl}-ethanesulfonic acid

Methyl 2-amino-5-chlorobenzoate (compound A) (4.0 g) was dissolved in anhydrous methylene chloride (80.0 ml). Subsequently, pyridine (2.8 ml) and 3-(chloromethyl)benzoyl chloride (compound B) (5.0 g) were added to the solution at room temperature, and the mixture was stirred at that temperature for 2 hr. After the completion of the reaction, distilled water was added thereto, and the mixture was subjected to separatory extraction with chloroform. The organic layer was washed with a saturated aqueous sodium chloride solution and saturated brine, was dried over sodium sulfate, and was then concentrated to give methyl 5-chloro-2-[3-(chloromethyl)benzoyl]aminobenzoate (3.32 g, yield 100%) as a useful intermediate.

Subsequently, methyl 5-chloro-2-[3-(chloromethyl)benzoyl]aminobenzoate (1.8 g) was dissolved in anhydrous methylene chloride. Triethylamine (1.5 ml) and 2-mercaptoethanesulfonic acid sodium salt (compound B′) (1.3 g) were added to the solution at room temperature, and the mixture was stirred at 40° C. for 4 days. After the completion of the reaction, distilled water was added thereto at room temperature, and the mixture was subjected to separatory extraction with chloroform. The organic layer was washed with a saturated aqueous sodium chloride solution, was dried over sodium sulfate, and was then concentrated. The residue was purified by column chromatography on silica gel to give 5-chloro-2-[3-(2-sulfo-ethylsulfanylmethyl)-benzoylamino]-benzoic acid methyl ester (1.08 g, yield 46.1%) as a useful intermediate.

5-Chloro-2-[3-(2-sulfo-ethylsulfanylmethyl)-benzoylamino]-benzoic acid methyl ester (1.27 g) produced by the above reaction was dissolved in ethanol (15.0 ml). Hydrazine monohydrate (2.0 ml) was added to the solution at room temperature, and the mixture was stirred at 40° C. for 12 hr. After the completion of the reaction, the reaction solution was allowed to cool at room temperature. The reaction solution as such was then concentrated, and the residue was purified by column chromatography on silica gel to give 2-[3-(4-chloro-2-hydrazinocarbonyl-phenylcarbamoyl)-benzylsulfanyl]-ethanesulfonic acid as a hydrazine compound (820 mg, yield 67.2%).

2-[3-(4-Chloro-2-hydrazinocarbonyl-phenylcarbamoyl)-benzylsulfanyl]-ethanesulfonic acid (50.0 mg) was dissolved in anhydrous toluene (1.0 ml). Subsequently, 4-chloro-3-trifluoromethylbenzaldehyde (compound C) (50.0 μl) was added to the solution at room temperature, and the mixture was heated under reflux with stirring for 12 hr. After the completion of the reaction, the reaction solution was allowed to cool at room temperature, distilled water was added thereto, and the mixture was subjected to separatory extraction with chloroform. The organic layer was washed with a saturated aqueous sodium chloride solution and saturated brine, was dried over sodium sulfate, and was then concentrated. The residue was purified by column chromatography on silica gel and was dried through a vacuum pump to give the title compound 709 (47.2 mg, yield 56.0%).

¹H-NMR (CD₃OD, 400 MHz): δ 8.52 (1H, d, J=9.0 Hz), 7.38-8.40 (10H, m), 3.89 (2H, s), 2.94-3.06 (2H, m), 2.70-2.88 (2H, m)

Mass spectrometric value (ESI-MS) 632 (M−1)

Compound 710 3-{[(2-Diethylamino-ethyl)-methyl-amino]-methyl}-N-[4-methyl-2-(4-methyl-benzylidene-hydrazinocarbonyl)-thiophen-3-yl]-benzamide

The title compound 710 was produced in the same manner as in Example 8.

¹H-NMR (CD₃OD, 400 MHz): δ 8.18 (1H, bs), 7.88-8.03 (3H, m), 7.64-7.70 (2H, m), 7.59 (1H, d, J=7.8 Hz), 7.46-7.55 (1H, m), 7.25 (2H, bs), 3.64 (2H, s), 2.72 (2H, bs), 2.53-2.65 (6H, m), 2.37 (3H, s), 2.28 (3H, s), 2.24 (3H, s), 1.04 (6H, t, J=7.3 Hz)

Mass spectrometric value (ESI-MS) 520 (M+1)

Compound 711 3-{[(2-Diethylamino-ethyl)-methyl-amino]-methyl}-N-[2-(3,4-dimethyl-benzylidene-hydrazinocarbonyl)-4-methyl-thiophen-3-yl]-benzamide

The title compound 711 was produced in the same manner as in Example 8.

¹H-NMR (CD₃OD, 400 MHz): δ 7.88-8.18 (3H, m), 7.37-7.64 (5H, m), 7.19 (1H, s), 3.63 (2H, s), 2.67-2.75 (2H, m), 2.53-2.65 (6H, m), 2.20-2.35 (12H, m), 0.98-1.10 (6H, m)

Mass spectrometric value (ESI-MS) 532 (M−1), 534 (M+1)

Compound 712 3-{[(2-Diethylamino-ethyl)-methyl-amino]-methyl}-N-[2-(4-methoxy-benzylidene-hydrazinocarbonyl)-4-methyl-thiophen-3-yl]-benzamide

The title compound 712 was produced in the same manner as in Example 8.

¹H-NMR (CD₃OD, 400 MHz): δ 7.90-8.03 (3H, m), 7.72 (2H, d, J=8.1 Hz), 7.59 (1H, d, J=7.3 Hz), 7.38-7.56 (2H, m), 6.97 (2H, bs), 3.84 (2H, s), 3.64 (2H, s), 2.67-2.75 (2H, m), 2.53-2.65 (6H, m), 2.27 (3H, s), 2.24 (3H, s), 1.00-1.10 (6H, m)

Mass spectrometric value (ESI-MS) 534 (M−1), 536 (M+1)

Compound 713 N-[4-Bromo-2-(3-fluoro-benzylidene-hydrazinocarbonyl)-phenyl]-4-[(2-morpholin-4-yl-ethylamino)-methyl]-benzamide

The title compound 713 was produced in the same manner as in Example 8.

¹H-NMR (CDCl₃, 400 MHz): δ 8.43 (2H, bs), 7.99 (2H, d, J=7.8 Hz), 7.68 (1H, s), 7.36-7.60 (6H, m), 7.13 (1H, ddd, J=8.3 Hz, J=8.3 Hz, J=2.0 Hz), 3.89 (2H, s), 3.68-3.73 (4H, m), 2.72 (2H, t, J=5.9 Hz), 2.53 (2H, t, J=6.0 Hz), 2.43 (4H, t, J=4.4 Hz)

Mass spectrometric value (ESI-MS) 582 (M−1)

Compound 714 N-[4-Bromo-2-(4-chloro-3-trifluoromethyl-benzylidene-hydrazinocarbonyl)-phenyl]-4-[(2-morpholin-4-yl-ethylamino)-methyl]-benzamide

The title compound 714 was produced in the same manner as in Example 8.

¹H-NMR (CDCl₃, 400 MHz): δ 8.51 (1H, s), 8.31 (1H, d, J=8.3 Hz), 8.06 (1H, s), 7.99 (3H, d, J=7.6 Hz), 7.65 (1H, s), 7.58 (1H, d, J=8.3 Hz), 7.47 (3H, d, J=7.7 Hz), 3.89 (2H, s), 3.71 (4H, t, J=4.5 Hz), 2.71 (2H, t, J=6.0 Hz), 2.53 (2H, t, J=6.0 Hz), 2.43 (4H, bs)

Mass spectrometric value (ESI-MS) 664, 666 (M−1)

Compound 715 N-[4-Bromo-2-(4-methoxy-benzylidene-hydrazinocarbonyl)-phenyl]-4-[(2-morpholin-4-yl-ethylamino)-methyl]-benzamide

The title compound 715 was produced in the same manner as in Example 8.

¹H-NMR (CDCl₃, 400 MHz): δ 8.43 (1H, d, J=8.8 Hz), 8.38 (1H, s), 7.98 (2H, d, J=8.1 Hz), 7.68-7.77 (3H, m), 7.48 (1H, d, J=8.8 Hz), 7.41 (2H, d, J=8.8 Hz), 6.90 (2H, d, J=8.8 Hz), 3.86 (2H, s), 3.81 (3H, s), 3.68-3.72 (4H, m), 2.69 (2H, t, J=6.0 Hz), 2.51 (2H, t, J=6.0 Hz), 2.38-2.45 (4H, m)

Mass spectrometric value (ESI-MS) 592 (M−1)

Compound 716 N-[4-Bromo-2-(3-methoxy-benzylidene-hydrazinocarbonyl)-phenyl]-4-[(2-morpholin-4-yl-ethylamino)-methyl]-benzamide

The title compound 716 was produced in the same manner as in Example 8.

¹H-NMR (CDCl₃, 400 MHz): δ 8.40-8.46 (2H, m), 7.98 (2H, d, J=7.8 Hz), 7.71 (1H, s), 7.49 (1H, d, J=8.5 Hz), 7.42 (2H, d, J=8.0 Hz), 7.35 (1H, s), 7.30 (2H, d, J=5.6 Hz), 3.86 (2H, s), 3.84 (3H, s), 3.70 (4H, t, J=4.6 Hz), 2.69 (2H, t, J=4.6 Hz), 2.51 (2H, t, J=5.8 Hz), 2.40-2.47 (4H, m)

Mass spectrometric value (ESI-MS) 596 (M+1)

Compound 717 N-[4-Bromo-2-(3,4-dimethyl-benzylidene-hydrazinocarbonyl)-phenyl]-4-[4-(4-fluoro-phenyl)-piperazin-1-ylmethyl]-benzamide

The title compound 717 was produced in the same manner as in Example 8.

¹H-NMR (CDCl₃, 400 MHz): δ 8.57 (1H, d, J=9.0 Hz), 8.28 (1H, s), 8.00 (2H, d, J=7.6 Hz), 7.55-7.73 (3H, m), 7.48 (3H, d, J=8.1 Hz), 7.18 (1H, d, J=7.8 Hz), 6.93-6.98 (2H, m), 6.85-6.90 (2H, m), 3.63 (2H, s), 3.13 (4H, t, J=4.6 Hz), 2.62 (4H, bs), 2.30 (3H, s), 2.29 (3H, s)

Mass spectrometric value (ESI-MS) 642 (M−1)

Compound 718 4-{[Bis-(2-hydroxy-propyl)-amino]-methyl}-N-[4-bromo-2-(3-methyl-benzylidene-hydrazinocarbonyl)-phenyl]-benzamide

The title compound 718 was produced in the same manner as in Example 8.

¹H-NMR (CDCl₃, 400 MHz): δ 8.53 (1H, d, J=8.6 Hz), 8.35 (1H, s), 8.02 (2H, d, J=7.3 Hz), 7.70 (2H, s), 7.53-7.60 (2H, m), 7.45 (2H, d, J=8.1 Hz), 7.32 (1H, dd, J=7.4 Hz, J=7.4 Hz), 3.60-3.99 (4H, m), 2.42-2.66 (4H, m), 2.39 (3H, s), 1.12 (6H, d, J=6.1 Hz)

Mass spectrometric value (ESI-MS) 581 (M+1)

Compound 719 4-{[Bis-(2-hydroxy-propyl)-amino]-methyl}-N-[4-bromo-2-(4-fluoro-benzylidene-hydrazinocarbonyl)-phenyl]-benzamide

The title compound 719 was produced in the same manner as in Example 8.

¹H-NMR (CDCl₃, 400 MHz): δ 8.53 (1H, bs), 8.37 (1H, bs), 8.00 (2H, bs), 7.81 (2H, bs), 7.70 (1H, bs), 7.40-7.60 (3H, m), 7.05-7.15 (2H, m), 3.83-3.98 (2H, m), 3.65-3.78 (2H, m), 2.45-2.60 (4H, m), 1.20-1.30 (3H, m), 1.06-1.16 (3H, m)

Mass spectrometric value (ESI-MS) 587 (M+1)

Compound 720 4-{[Bis-(2-hydroxy-propyl)-amino]-methyl}-N-[4-bromo-2-(3-fluoro-benzylidene-hydrazinocarbonyl)-phenyl]-benzamide

The title compound 720 was produced in the same manner as in Example 8.

¹H-NMR (CDCl₃, 400 MHz): δ 8.45-8.54 (1H, m), 8.39 (1H, s), 8.00 (2H, d, J=8.3 Hz), 7.36-7.74 (7H, m), 7.10-7.20 (1H, m), 3.80-4.02 (4H, m), 2.47-2.60 (4H, m), 1.12 (6H, d, J=6.4 Hz)

Mass spectrometric value (ESI-MS) 585 (M+1)

Compound 721 4-{[Bis-(2-hydroxy-propyl)-amino]-methyl}-N-[4-bromo-2-(4-chloro-3-trifluoromethyl-benzylidene-hydrazinocarbonyl)-phenyl]-benzamide

The title compound 721 was produced in the same manner as in Example 8.

¹H-NMR (CDCl₃, 400 MHz): δ 8.46 (2H, bs), 7.95-8.08 (3H, m), 7.45-7.75 (4H, m), 7.13-7.20 (2H, m), 3.60-4.03 (4H, m), 2.47-2.68 (4H, m), 1.12 (6H, d, J=6.1 Hz)

Mass spectrometric value (ESI-MS) 667, 669 (M−1)

Compound 722 4-{[Bis-(2-hydroxy-propyl)-amino]-methyl}-N-[4-bromo-2-(4-methoxy-benzylidene-hydrazinocarbonyl)-phenyl]-benzamide

The title compound 722 was produced in the same manner as in Example 8.

¹H-NMR (CDCl₃, 400 MHz): δ 8.37-8.47 (2H, m), 7.98 (2H, d, J=7.8 Hz), 7.70-7.74 (3H, m), 7.38-7.53 (3H, m), 6.90 (2H, d, J=8.8 Hz), 3.77-3.95 (4H, m), 3.81 (3H, s), 2.42-2.64 (4H, m), 1.08-1.14 (6H, m)

Mass spectrometric value (ESI-MS) 597 (M+1)

Compound 723 4-{[Bis-(2-hydroxy-propyl)-amino]-methyl}-N-[4-bromo-2-(3-methoxy-benzylidene-hydrazinocarbonyl)-phenyl]-benzamide

The title compound 723 was produced in the same manner as in Example 8.

¹H-NMR (CDCl₃, 400 MHz): δ 8.57 (1H, d, J=8.5 Hz), 8.34 (1H, s), 8.00 (2H, d, J=7.1 Hz), 7.72 (1H, s), 7.55-7.62 (1H, m), 7.46 (2H, d, J=8.0 Hz), 7.30-7.40 (3H, m), 6.95-7.02 (1H, m), 3.80-4.00 (4H, m), 3.86 (3H, s), 2.40-2.65 (4H, m), 1.09-1.15 (6H, m)

Mass spectrometric value (ESI-MS) 597 (M−1)

Compound 724 N-[4-Bromo-2-(3,4-dimethyl-benzylidene-hydrazinocarbonyl)-phenyl]-4-({[2-hydroxy-2-(4-hydroxy-phenyl)-ethyl]-methyl-amino}-methyl)-benzamide

The title compound 724 was produced in the same manner as in Example 8.

¹H-NMR (CD₃OD, 400 MHz): δ 8.56-8.66 (1H, m), 7.96 (2H, dd, J=2.2 Hz, J=8.3 Hz), 7.87 (1H, d, J=2.4 Hz), 7.65-7.78 (3H, m), 7.46-7.56 (3H, m), 7.13-7.22 (3H, m), 6.72-6.78 (2H, m), 4.80-4.90 (1H, m), 3/5-3.90 (2H, m), 2.73-2.82 (1H, m), 2.58-2.66 (1H, m), 2.40-2.45 (3H, m), 2.28-2.32 (6H, m)

Mass spectrometric value (ESI-MS) 629 (M−1)

Compound 725 N14-Bromo-2-(3-fluoro-benzylidene-hydrazinocarbonyl)-phenyl]-4-({[2-hydroxy-2-(4-hydroxy-phenyl)-ethyl]-methyl-amino}-methyl)-benzamide

The title compound 725 was produced in the same manner as in Example 8.

¹H-NMR (CD₃OD, 400 MHz): δ 8.61 (1H, d, J=8.0 Hz), 8.36 (1H, s), 8.07 (1H, d, J=2.2 Hz), 7.92 (2H, d, J=2.2 Hz), 7.56 (1H, dd, J=2.2 Hz, J=9.0 Hz), 7.70 (1H, d, J=9.3 Hz), 7.60 (1H, d, J=7.8 Hz), 7.42-7.49 (3H, m), 7.10-7.24 (3H, m), 6.75 (2H, d, J=8.6 Hz), 4.70-4.75 (1H, m), 3.68 (2H, d, J=4.4 Hz), 2.67 (1H, dd, J=12.7 Hz, J=8.5 Hz), 2.50 (1H, dd, J=4.9 Hz, J=12.7 Hz), 2.33 (3H, s)

Mass spectrometric value (ESI-MS) 619 (M−1)

Compound 726 N-[4-Bromo-2-(4-chloro-3-trifluoromethyl-benzylidene-hydrazinocarbonyl)-phenyl]-4-({[2-hydroxy-2-(4-hydroxy-phenyl)-ethyl]-methyl-amino}-methyl)-benzamide

The title compound 726 was produced in the same manner as in Example 8.

¹H-NMR (CD₃OD, 400 MHz): δ 8.61 (1H, d, J=9.0 Hz), 8.40 (1H, s), 8.34 (1H, s), 8.04-8.10 (2H, m), 7.90-7.95 (2H, m), 7.77 (1H, dd, J=9.0 Hz, J=2.4 Hz), 7.69 (1H, d, J=8.3 Hz), 7.45 (2H, d, J=8.3 Hz), 7.13 (2H, d, J=8.6 Hz), 6.75 (2H, d, J=8.6 Hz), 4.70-4.80 (1H, m), 3.70 (2H, d, J=4.4 Hz), 2.68 (1H, dd, J=8.3 Hz, J=12.8 Hz), 2.52 (1H, dd, J=4.6 Hz, J=12.7 Hz), 2.36 (3H, s)

Mass spectrometric value (ESI-MS) 701, 703 (M−1)

Compound 727 N-[4-Bromo-2-(3-methoxy-benzylidene-hydrazinocarbonyl)-phenyl]-4-({[2-hydroxy-2-(4-hydroxy-phenyl)-ethyl]-methyl-amino}-methyl)-benzamide

The title compound 727 was produced in the same manner as in Example 8.

¹H-NMR (CD₃OD, 400 MHz): δ 8.63 (1H, d, J=9.0 Hz), 8.34 (1H, s), 8.07 (1H, d, J=2.4 Hz), 7.94 (2H, d, J=8.3 Hz), 7.75 (1H, dd, J=8.8 Hz, J=2.2 Hz), 7.61 (1H, bs), 7.44 (2H, d, J=8.3 Hz), 7.26-7.36 (2H, m), 7.13 (2H, d, J=8.3 Hz), 6.97-7.03 (1H, m), 6.76 (2H, d, J=8.6 Hz), 4.72-4.82 (1H, m), 3.84 (3H, s), 3.76 (2H, d, J=5.8 Hz), 2.72 (1H, dd, J=8.6 Hz, J=13.0 Hz), 2.41 (3H, s), 2.57 (1H, dd, J=4.9 Hz, J=13.0 Hz)

Mass spectrometric value (ESI-MS) 629 (M−1)

Compound 728 N-[4-Bromo-2-(4-methyl-benzylidene-hydrazinocarbonyl)-phenyl]-4-[4-(2-morpholin-4-yl-2-oxo-ethyl)-piperazin-1-ylmethyl]-benzamide

The title compound 728 was produced in the same manner as in Example 8.

¹H-NMR (CD₃OD, 400 MHz): δ 8.49 (1H, d, J=9.0 Hz), 8.41 (1H, s), 7.97 (2H, d, J=7.8 Hz), 7.73 (1H, s), 7.68 (1H, d, J=7.6 Hz), 7.51 (1H, d, J=7.8 Hz), 7.41 (2H, d, J=7.8 Hz), 7.19-7.23 (3H, m), 3.47-3.75 (10H, m), 3.16 (2H, s), 2.40-2.56 (8H, m), 2.36 (3H, s)

Mass spectrometric value (ESI-MS) 659 (M−1)

Compound 729 N-[4-Bromo-2-(3-methyl-benzylidene-hydrazinocarbonyl)-phenyl]-4-[4-(2-morpholin-4-yl-2-oxo-ethyl)-piperazin-1-ylmethyl]-benzamide

The title compound 729 was produced in the same manner as in Example 8.

¹H-NMR (CD₃OD, 400 MHz): δ 8.48 (1H, d, J=8.8 Hz), 8.42 (1H, s), 7.97 (2H, d, J=7.8 Hz), 7.66-7.75 (2H, m), 7.49-7.56 (2H, m), 7.41 (2H, d, J=7.8 Hz), 7.20-7.32 (2H, m), 3.48-3.76 (10H, m), 3.16 (2H, s), 2.40-2.56 (8H, m), 2.38 (3H, s)

Mass spectrometric value (ESI-MS) 661 (M−1)

Compound 730 N-[4-Bromo-2-(4-fluoro-benzylidene-hydrazinocarbonyl)-phenyl]-4-[4-(2-morpholin-4-yl-2-oxo-ethyl)-piperazin-1-ylmethyl]-benzamide

The title compound 730 was produced in the same manner as in Example 8.

¹H-NMR (CD₃OD, 400 MHz): δ 8.48 (1H, d, J=9.0 Hz), 8.43 (1H, s), 7.97 (2H, d, J=7.8 Hz), 7.76-7.87 (2H, m), 7.68-7.73 (1H, m), 7.49-7.57 (1H, m), 7.42 (2H, d, J=7.8 Hz), 7.11 (2H, dd, J=8.5 Hz, J=8.5 Hz), 3.49-3.76 (10H, m), 3.16 (2H, s), 2.40-2.65 (8H, m)

Mass spectrometric value (ESI-MS) 665 (M−1)

Compound 731 N-[4-Bromo-2-(3-fluoro-benzylidene-hydrazinocarbonyl)-phenyl]-4-[4-(2-morpholin-4-yl-2-oxo-ethyl)-piperazin-1-ylmethyl]-benzamide

The title compound 731 was produced in the same manner as in Example 8.

¹H-NMR (CD₃OD, 400 MHz): δ 8.42-8.52 (2H, m), 7.96 (2H, d, J=7.8 Hz), 7.73 (1H, s), 7.46-7.60 (3H, m), 7.33-7.44 (3H, m), 7.11 (1H, ddd, J=2.4 Hz, J=8.3 Hz, J=8.3 Hz), 3.48-3.76 (10H, m), 3.15 (2H, s), 2.40-2.60 (8H, m)

Mass spectrometric value (ESI-MS) 665 (M−1)

Compound 732 N-[4-Bromo-2-(3-methoxy-benzylidene-hydrazinocarbonyl)-phenyl]-4-[4-(2-morpholin-4-yl-2-oxo-ethyl)-piperazin-1-ylmethyl]-benzamide

The title compound 732 was produced in the same manner as in Example 8.

¹H-NMR (CD₃OD, 400 MHz): δ 8.50 (2H, s, J=9.0 Hz), 8.45 (1H, s), 7.95 (2H, d, J=7.8 Hz), 7.78 (1H, s), 7.51 (1H, d, J=8.8 Hz), 7.25-7.43 (3H, m), 6.90-7.00 (2H, m), 3.83 (3H, s), 3.48-3.75 (10H, m), 3.16 (2H, s), 2.40-2.60 (8H, m)

Mass spectrometric value (ESI-MS) 675, 677 (M−1)

Compound 733 4-{[Bis-(2-ethoxy-ethyl)-amino]-methyl}-N-[4-bromo-2-(3,4-dimethyl-benzylidene-hydrazinocarbonyl)-phenyl]-benzamide

The title compound 733 was produced in the same manner as in Example 8.

¹H-NMR (CD₃OD, 400 MHz): δ 8.36-8.46 (2H, m), 7.98 (2H, d, J=8.0 Hz), 7.66 (2H, d, J=10.0 Hz), 7.45-7.51 (4H, m), 7.17 (1H, d, J=8.1 Hz), 3.79 (2H, s), 3.52 (4H, t, J=6.1 Hz), 3.46 (4H, q, J=7.0 Hz), 2.76 (4H, t, J=6.0 Hz), 2.29 (3H, s), 2.27 (3H, s), 1.19 (6H, t, J=7.0 Hz)

Mass spectrometric value (ESI-MS) 622, 624 (M−1)

Compound 734 4-{[Bis-(2-ethoxy-ethyl)-amino]-methyl}-N-[4-bromo-2-(4-methyl-benzylidene-hydrazinocarbonyl)-phenyl]-benzamide

The title compound 734 was produced in the same manner as in Example 8.

¹H-NMR (CD₃OD, 400 MHz): δ 8.45 (1H, s), 8.36 (1H, d, J=8.8 Hz), 7.98 (2H, d, J=7.3 Hz), 7.65-7.71 (3H, m), 7.45-7.48 (3H, m), 7.20 (2H, d, J=7.8 Hz), 3.79 (2H, s), 3.53 (4H, t, J=6.2 Hz), 3.46 (4H, q, J=7.9 Hz), 2.76 (4H, t, J=6.1 Hz), 2.35 (3H, s), 1.19 (6H, t, J=7.1 Hz)

Mass spectrometric value (ESI-MS) 607, 609 (M−1)

Compound 735 4-{[Bis-(2-ethoxy-ethyl)-amino]-methyl}-N-[4-bromo-2-(3-methyl-benzylidene-hydrazinocarbonyl)-phenyl]-benzamide

The title compound 735 was produced in the same manner as in Example 8.

¹H-NMR (CDCl₃, 400 MHz): δ 8.47 (1H, s), 8.34 (1H, d, J=8.8 Hz), 7.98 (2H, d, J=8.0 Hz), 7.68 (2H, d, J=8.3 Hz), 7.54 (1H, d, J=7.3 Hz), 7.42-7.50 (3H, m), 7.20-7.34 (2H, m), 3.78 (2H, s), 3.52 (4H, t, J=6.1 Hz), 3.46 (4H, q, J=7.0 Hz), 2.76 (4H, t, J=6.2 Hz), 2.38 (3H, s), 1.19 (6H, t, J=7.0 Hz)

Mass spectrometric value (ESI-MS) 609 (M−1)

Compound 736 4-{[Bis-(2-ethoxy-ethyl)-amino]-methyl}-N-[4-bromo-2-(4-fluoro-benzylidene-hydrazinocarbonyl)-phenyl]-benzamide

The title compound 736 was produced in the same manner as in Example 8.

¹H-NMR (CDCl₃, 400 MHz): δ 8.48 (1H, s), 8.31 (1H, d, J=8.8 Hz), 7.98 (2H, d, J=8.0 Hz), 7.81 (2H, dd, J=6.5 Hz, J=6.5 Hz), 7.64 (1H, s), 7.42-7.51 (3H, m), 7.10 (2H, dd, J=8.7 Hz, J=8.7 Hz), 3.79 (2H, s), 3.53 (4H, t, J=6.2 Hz), 3.67 (4H, q, J=7.0 Hz), 2.76 (4H, t, J=6.1 Hz), 1.19 (6H, t, J=6.9 Hz)

Mass spectrometric value (ESI-MS) 635 (M+23)

Compound 737 4-{[Bis-(2-ethoxy-ethyl)-amino]-methyl}-N-[4-bromo-2-(3-fluoro-benzylidene-hydrazinocarbonyl)-phenyl]-benzamide

The title compound 737 was produced in the same manner as in Example 8.

¹H-NMR (CDCl₃, 400 MHz): δ 8.50 (1H, s), 8.29 (1H, d, J=8.8 Hz), 7.98 (2H, d, J=8.0 Hz), 7.30-7.76 (7H, m), 7.11 (1H, ddd, J=2.0 Hz, J=8.3 Hz, J=8.3 Hz), 3.80 (2H, s), 3.53 (4H, t, J=6.2 Hz), 3.47 (4H, q, J=6.2 Hz), 2.76 (4H, t, J=6.2 Hz), 1.19 (6H, t, J=6.9 Hz)

Mass spectrometric value (ESI-MS) 635 (M+23)

Compound 738 4-{[Bis-(2-ethoxy-ethyl)-amino]-methyl}-N-[4-bromo-2-(4-chloro-3-trifluoromethyl-benzylidene-hydrazinocarbonyl)-phenyl]-benzamide

The title compound 738 was produced in the same manner as in Example 8.

¹H-NMR (CDCl₃, 400 MHz): δ 8.55 (1H, s), 8.24 (1H, d, J=8.0 Hz), 8.07 (1H, s), 7.95-8.04 (3H, m), 7.62 (1H, s), 7.57 (1H, d, J=8.3 Hz), 7.50 (2H, d, J=8.3 Hz), 7.43 (1H, d, J=8.6 Hz), 3.81 (2H, s), 3.53 (4H, t, J=6.1 Hz), 3.47 (4H, q, J=7.0 Hz), 2.76 (4H, t, J=6.0 Hz), 1.19 (6H, t, J=7.1 Hz)

Mass spectrometric value (ESI-MS) 721 (M+23)

Compound 739 4-{[Bis-(2-ethoxy-ethyl)-amino]-methyl}-N-[4-bromo-2-(4-methoxy-benzylidene-hydrazinocarbonyl)-phenyl]-benzamide

The title compound 739 was produced in the same manner as in Example 8.

¹H-NMR (CDCl₃, 400 MHz): δ 8.53 (1H, d, J=9.0 Hz), 8.35-8.45 (1H, m), 7.96 (2H, dd, J=7.6 Hz, 7.6 Hz), 7.75 (1H, d, J=8.5 Hz), 7.67 (1H, s), 7.53 (1H, ddd, J=1.9 Hz, J=8.8 Hz, J=8.8 Hz), 7.42-7.50 (3H, m), 5.92 (2H, d, J=8.8 Hz), 3.83 (3H, s), 3.78 (2H, s), 3.52 (4H, t, J=6.1 Hz), 3.46 (4H, q, J=7.1 Hz), 2.75 (4H, t, J=5.5 Hz), 1.19 (6H, t, J=7.1 Hz)

Mass spectrometric value (ESI-MS) 625 (M−1)

Compound 740 4-{[Bis-(2-ethoxy-ethyl)-amino]-methyl}-N-[4-bromo-2-(3-methoxy-benzylidene-hydrazinocarbonyl)-phenyl]-benzamide

The title compound 740 was produced in the same manner as in Example 8.

¹H-NMR (CDCl₃, 400 MHz): δ 8.47 (1H, s), 8.36 (1H, d, J=8.8 Hz), 7.97 (2H, d, J=8.8 Hz), 7.68 (1H, s), 7.47 (3H, d, J=8.1 Hz), 7.37 (1H, s), 7.27-7.34 (2H, m), 6.92-6.98 (1H, m), 3.85 (3H, s), 3.78 (2H, s), 3.52 (4H, t, J=6.1 Hz), 3.46 (4H, q, J=7.0 Hz), 2.75 (4H, t, J=6.0 Hz), 1.18 (6H, t, J=7.0 Hz)

Mass spectrometric value (ESI-MS) 649 (M+23)

Compound 741 N-[4-Bromo-2-(4-methyl-benzylidene-hydrazinocarbonyl)-phenyl]-4-[4-(2-hydroxy-ethyl)-piperidin-1-ylmethyl]-benzamide

The title compound 741 was produced in the same manner as in Example 8.

¹H-NMR (DMSO-d₆, 400 MHz): δ 8.51 (1H, d, J=9.0 Hz), 8.41 (1H, s), 8.09 (1H, d, J=2.2 Hz), 7.89 (2H, d, J=8.0 Hz), 7.81 (1H, dd, J=2.4 Hz, J=9.0 Hz), 7.65 (2H, d, J=8.3 Hz), 7.49 (2H, d, J=8.0 Hz), 7.29 (2H, d, J=7.8 Hz), 4.29 (1H, t, J=5.1 Hz), 3.52 (2H, bs), 3.38-3.46 (2H, m), 2.78 (2H, d, J=11.0 Hz), 2.36 (3H, s), 1.92 (2H, t, J=11.1 Hz), 1.61 (2H, d, J=6.1 Hz), 1.30-1.40 (3H, m), 1.10-1.20 (2H, m)

Mass spectrometric value (ESI-MS) 577 (M−1)

Compound 742 N-[4-Bromo-2-(3-methyl-benzylidene-hydrazinocarbonyl)-phenyl]-4-[4-(2-hydroxy-ethyl)-piperidin-1-ylmethyl]-benzamide

The title compound 742 was produced in the same manner as in Example 8.

¹H-NMR (DMSO-d₆, 400 MHz): δ 8.51 (1H, d, J=8.8 Hz), 8.41 (1H, s), 8.10 (1H, d, J=8.3 Hz), 7.88 (2H, d, J=2.2 Hz), 7.81 (1H, dd, J=2.2 Hz, J=9.0 Hz), 7.59 (1H, s), 7.53 (1H, d, J=7.6 Hz), 7.49 (3H, d, J=7.6 Hz), 7.36 (1H, dd, J=7.6 Hz, J=7.6 Hz), 7.28 (1H, d, J=7.6 Hz), 4.29 (1H, t, J=5.1 Hz), 3.52 (2H, bs), 3.38-3.45 (2H, m), 2.77 (2H, d, J=11.2 Hz), 2.37 (3H, s), 1.92 (2H, t, J=10.6 Hz), 1.60 (2H, d, J=6.1 Hz), 1.30-1.40 (3H, m), 1.10-1.21 (2H, m)

Mass spectrometric value (ESI-MS) 575 (M−1)

Compound 743 N-[4-Bromo-2-(4-fluoro-benzylidene-hydrazinocarbonyl)-phenyl]-4-[4-(2-hydroxy-ethyl)-piperidin-1-ylmethyl]-benzamide

The title compound 743 was produced in the same manner as in Example 8.

¹H-NMR (DMSO-d₆, 400 MHz): δ 8.50 (1H, d, J=9.0 Hz), 8.45 (1H, s), 8.09 (1H, d, J=2.4 Hz), 7.88 (2H, d, J=8.0 Hz), 7.78-7.85 (3H, m), 7.49 (2H, d, J=8.3 Hz), 7.32 (2H, dd, J=8.8 Hz, J=8.8 Hz), 4.29 (1H, t, J=5.1 Hz), 3.52 (2H, bs), 3.38-3.45 (2H, m), 2.77 (2H, d, J=11.2 Hz), 1.92 (2H, t, J=10.7 Hz), 1.60 (2H, d, J=6.1 Hz), 1.30-1.40 (3H, m), 1.10-1.20 (2H, m)

Mass spectrometric value (ESI-MS) 581 (M−1)

Compound 744 N-[4-Bromo-2-(3-fluoro-benzylidene-hydrazinocarbonyl)-phenyl]-4-[4-(2-hydroxy-ethyl)-piperidin-1-ylmethyl]-benzamide

The title compound 744 was produced in the same manner as in Example 8.

¹H-NMR (DMSO-d₆, 400 MHz): δ 8.49 (1H, d, J=8.8 Hz), 8.44 (1H, s), 8.09 (1H, d, J=2.2 Hz), 7.88 (2H, d, J=8.0 Hz), 7.78-7.84 (1H, m), 7.47-7.63 (5H, m), 7.25-7.35 (1H, m), 4.27 (1H, t, J=5.1 Hz), 3.52 (2H, s), 3.35-3.46 (2H, m), 2.77 (2H, d, J=11.2 Hz), 1.92 (2H, dd, J=11.0 Hz, J=11.0 Hz), 1.61 (2H, d, J=11.7 Hz), 1.30-1.40 (3H, m), 1.08-1.22 (2H, m)

Mass spectrometric value (ESI-MS) 580 (M−1), 583 (M+1)

Compound 745 N-[4-Bromo-2-(4-chloro-3-trifluoromethyl-benzylidene-hydrazinocarbonyl)-phenyl]-4-[4-(2-hydroxy-ethyl)-piperidin-1-ylmethyl]-benzamide

The title compound 745 was produced in the same manner as in Example 8.

¹H-NMR (DMSO-d₆, 400 MHz): δ 8.49 (1H, s), 8.44 (1H, d, J=8.8 Hz), 8.18 (1H, s), 8.05-8.10 (2H, m), 7.88 (2H, d, J=8.1 Hz), 7.79-7.85 (2H, m), 7.49 (2H, d, J=8.1 Hz), 4.29 (1H, bs), 3.52 (2H, bs), 3.38-3.45 (2H, m), 2.78 (2H, d, J=11.2 Hz), 1.86-2.00 (2H, m), 1.60 (2H, d, J=12.2 Hz), 1.30-1.40 (3H, m), 1.08-1.22 (2H, m)

Mass spectrometric value (ESI-MS) 667 (M+1)

Compound 746 N-[4-Bromo-2-(3-methoxy-benzylidene-hydrazinocarbonyl)-phenyl]-4-[4-(2-hydroxy-ethyl)-piperidin-1-ylmethyl]-benzamide

The title compound 746 was produced in the same manner as in Example 8.

¹H-NMR (DMSO-d₆, 400 MHz): δ 8.48 (1H, d, J=8.8 Hz), 8.42 (1H, s), 8.09 (1H, d, J=2.0 Hz), 7.88 (2H, d, J=8.0 Hz), 7.78-7.83 (1H, m), 7.49 (2H, d, J=9.0 Hz), 7.39 (1H, dd, J=7.8 Hz, J=7.8 Hz), 7.28-7.33 (2H, m), 7.00-7.07 (1H, m), 4.29 (1H, t, J=5.0 Hz), 3.82 (3H, s), 3.52 (2H, bs), 3.37-3.46 (2H, m), 2.77 (2H, d, J=10.8 Hz), 1.86-1.98 (2H, m), 1.60 (2H, d, J=12.2 Hz), 1.30-1.40 (3H, m), 1.08-1.22 (2H, m)

Mass spectrometric value (ESI-MS) 593 (M−1)

Compound 747 N-[4-Bromo-2-(4-chloro-3-trifluoromethyl-benzylidene-hydrazinocarbonyl)-phenyl]-4-[(2-morpholin-4-yl-1-phenyl-ethylamino)-methyl]-benzamide

The title compound 747 was produced in the same manner as in Example 8.

¹H-NMR (CDCl₃, 400 MHz): δ 8.51 (1H, s), 8.33 (1H, d, J=8.0 Hz), 8.06 (1H, s), 7.99 (3H, d, J=7.8 Hz), 7.65 (1H, bs), 7.58 (1H, d, J=8.3 Hz), 7.49 (1H, d, J=7.6 Hz), 7.26-7.43 (7H, m), 3.84 (1H, d, J=14.2 Hz), 3.64-3.78 (6H, m), 3.57 (1H, d, J=14.2 Hz), 2.43-2.60 (3H, m), 2.29-2.40 (3H, m)

Mass spectrometric value (ESI-MS) 742 (M−1)

Compound 748 N-[4-Bromo-2-(4-methoxy-benzylidene-hydrazinocarbonyl)-phenyl]-4-[(2-morpholin-4-yl-1-phenyl-ethylamino)-methyl]-benzamide

The title compound 748 was produced in the same manner as in Example 8.

¹H-NMR (CDCl₃, 400 MHz): δ 8.44 (1H, d, J=8.8 Hz), 8.37 (1H, s), 7.99 (2H, d, J=7.8 Hz), 7.74 (2H, d, J=8.3 Hz), 7.69 (1H, s), 7.50 (1H, d, J=7.8 Hz), 7.34-7.42 (6H, m), 7.26-7.32 (1H, m), 6.91 (2H, d, J=8.8 Hz), 3.80-3.85 (1H, m), 3.82 (3H, s), 3.60-3.76 (5H, m), 3.50-3.57 (1H, m), 2.40-2.60 (3H, m), 2.28-2.34 (3H, m)

Mass spectrometric value (ESI-MS) 668 (M−1)

Compound 749 6-Bromo-2-{4-[(1,2-diethyl-pyrazolidin-4-ylamino)-methyl]-phenyl}-3-[(3,4-dimethyl-benzylidene)-amino]-3H-quinazolin-4-one

The title compound 749 was produced in the same manner as in Example 8.

¹H-NMR (CDCl₃, 400 MHz): δ 8.89 (1H, d, J=8.8 Hz), 8.73 (1H, s), 8.57 (1H, s), 8.03 (2H, d, J=8.0 Hz), 7.40-7.82 (5H, m), 7.10-7.25 (1H, m), 3.91 (2H, s), 3.56-3.70 (1H, m), 3.15-3.27 (2H, m), 2.70-2.85 (6H, m), 2.34 (6H, s), 1.11 (6H, t, J=7.1 Hz)

Mass spectrometric value (ESI-MS) 589 (M+1)

Compound 750 N-[4-Bromo-2-(3,4-dimethyl-benzylidene-hydrazinocarbonyl)-phenyl]-4-[(1,2-diethyl-pyrazolidin-4-ylamino)-methyl]-benzamide

The title compound 750 was produced in the same manner as in Example 8.

¹H-NMR (CDCl₃, 400 MHz): δ 8.42 (1H, d, J=9.0 Hz), 8.38 (1H, s), 7.99 (2H, d, J=8.1 Hz), 7.70 (1H, s), 7.62 (1H, s), 7.40-7.52 (4H, m), 7.15 (1H, d, J=7.8 Hz), 3.83 (2H, s), 3.56 (1H, tt, J=6.5 Hz, J=6.5 Hz), 3.12-3.20 (2H, m), 2.65-2.74 (6H, m), 2.28 (3H, s), 2.26 (3H, s), 1.09 (6H, t, J=7.2 Hz)

Mass spectrometric value (ESI-MS) 605 (M−1)

Compound 751 6-Bromo-2-{4-[(1,2-diethyl-pyrazolidin-4-ylamino)-methyl]-phenyl}-3-[(3-fluoro-benzylidene)-amino]-3H-quinazolin-4-one

The title compound 751 was produced in the same manner as in Example 8.

¹H-NMR (CDCl₃, 400 MHz): δ 8.90 (1H, d, J=8.8 Hz), 8.74 (1H, s), 8.59 (1H, s), 8.02 (2H, d, J=8.3 Hz), 7.42-7.65 (6H, m), 7.21 (1H, ddd, J=1.7 Hz, J=8.3 Hz, J=8.3 Hz), 3.89 (2H, s), 3.62 (1H, tt, J=6.4 Hz, J=6.4 Hz), 3.15-3.23 (2H, m), 2.65-2.80 (6H, m), 1.10 (6H, t, J=7.2 Hz)

Compound 752 N-[4-Bromo-2-(3-fluoro-benzylidene-hydrazinocarbonyl)-phenyl]-4-[(1,2-diethyl-pyrazolidin-4-ylamino)-methyl]-benzamide

The title compound 752 was produced in the same manner as in Example 8.

¹H-NMR (CDCl₃, 400 MHz): δ 8.46 (1H, s), 8.34 (1H, d, J=8.8 Hz), 7.99 (2H, d, J=7.8 Hz), 7.66 (1H, s), 7.34-7.62 (6H, m), 7.11 (1H, ddd, J=2.0 Hz, J=8.3 Hz, J=8.3 Hz), 3.85 (2H, s), 3.57 (1H, tt, J=6.5 Hz, J=6.5 Hz), 3.12-3.20 (2H, m), 2.64-2.74 (6H, m), 1.10 (6H, t, J=7.2 Hz)

Mass spectrometric value (ESI-MS) 595 (M−1)

Compound 753 6-Bromo-3-[(4-chloro-3-trifluoromethyl-benzylidene)-amino]-2-{4-[(1,2-diethyl-pyrazolidin-4-ylamino)-methyl]-phenyl}-3H-quinazolin-4-one

The title compound 753 was produced in the same manner as in Example 8.

¹H-NMR (CDCl₃, 400 MHz): δ 8.88 (1H, d, J=8.8 Hz), 8.75 (1H, s), 8.58 (1H, s), 7.92-8.05 (2H, m), 7.45-7.70 (6H, m), 3.89 (2H, s), 3.54-3.65 (1H, m), 3.12-3.22 (2H, m), 2.65-2.76 (6H, m), 1.10 (6H, t, J=7.2 Hz)

Mass spectrometric value (ESI-MS) 663 (M−1)

Compound 754 N-[4-Bromo-2-(4-chloro-3-trifluoromethyl-benzylidene-hydrazinocarbonyl)-phenyl]-4-[(1,2-diethyl-pyrazolidin-4-ylamino)-methyl]-benzamide

The title compound 754 was produced in the same manner as in Example 8.

¹H-NMR (CDCl₃, 400 MHz): δ 8.51 (1H, s), 8.31 (1H, d, J=8.1 Hz), 8.06 (1H, s), 7.99 (3H, d, J=7.8 Hz), 7.65 (1H, s), 7.58 (1H, d, J=8.3 Hz), 7.47 (3H, d, J=8.3 Hz), 3.86 (2H, s), 3.58 (1H, tt, J=6.3 Hz, J=6.3 Hz), 3.12-3.20 (2H, m), 2.65-2.75 (6H, m), 1.10 (6H, t, J=7.1 Hz)

Mass spectrometric value (ESI-MS) 681 (M+1)

Compound 755 6-Bromo-2-{4-[(1,2-diethyl-pyrazolidin-4-ylamino)-methyl]-phenyl}-3-[(4-methoxy-benzylidene)-amino]-3H-quinazolin-4-one

The title compound 755 was produced in the same manner as in Example 8.

¹H-NMR (CDCl₃, 400 MHz): δ 8.89 (1H, d, J=8.5 Hz), 8.71 (1H, s), 8.58 (1H, s), 8.03 (2H, d, J=8.3 Hz), 7.79 (2H, d, J=8.8 Hz), 7.60 (1H, d, J=2.2 Hz), 7.57 (1H, s), 7.49 (2H, d, J=8.3 Hz), 7.00 (2H, d, J=8.8 Hz), 3.89 (5H, s), 3.62 (1H, tt, J=6.2 Hz, J=6.2 Hz), 3.15-3.25 (2H, m), 2.65-2.80 (6H, m), 1.11 (6H, t, J=7.2 Hz)

Compound 756 N-[4-Bromo-2-(4-methoxy-benzylidene-hydrazinocarbonyl)-phenyl]-4-[(1,2-diethyl-pyrazolidin-4-ylamino)-methyl]-benzamide

The title compound 756 was produced in the same manner as in Example 8.

¹H-NMR (CDCl₃, 400 MHz): δ 8.46 (1H, d, J=8.8 Hz), 8.37 (1H, s), 7.98 (2H, d, J=7.8 Hz), 7.67-7.76 (3H, m), 7.49 (1H, d, J=7.6 Hz), 7.42 (2H, d, J=8.3 Hz), 6.91 (2H, d, J=8.8 Hz), 3.83 (2H, s), 3.82 (3H, s), 3.57 (1H, tt, J=6.3 Hz, J=6.3 Hz), 3.12-3.20 (2H, m), 2.65-2.75 (6H, m), 1.10 (6H, t, J=7.2 Hz)

Mass spectrometric value (ESI-MS) 607 (M−1)

Compound 757 N-[4-Bromo-2-(3,4-dimethyl-benzylidene-hydrazinocarbonyl)-phenyl]-4-{[3-(methyl-phenyl-amino)-propylamino]-methyl}-benzamide

The title compound 757 was produced in the same manner as in Example 8.

¹H-NMR (CDCl₃, 400 MHz): δ 8.35-8.45 (2H, m), 7.96 (2H, d, J=7.8 Hz), 7.71 (1H, s), 7.60 (1H, s), 7.43-7.48 (2H, m), 7.40 (2H, d, J=8.3 Hz), 7.17-7.23 (2H, m), 7.14 (1H, d, J=7.8 Hz), 6.65-6.73 (3H, m), 3.83 (2H, s), 3.38 (2H, t, J=7.2 Hz), 2.89 (3H, s), 2.68 (2H, t, J=7.0 Hz), 2.26 (3H, s), 2.25 (3H, s), 1.81 (2H, tt, J=7.1 Hz, J=7.1 Hz)

Mass spectrometric value (ESI-MS) 626 (M−1), 628 (M+1)

Compound 758 N-[4-Bromo-2-(4-methyl-benzylidene-hydrazinocarbonyl)-phenyl]-4-{[3-(methyl-phenyl-amino)-propylamino]-methyl}-benzamide

The title compound 758 was produced in the same manner as in Example 8.

¹H-NMR (CDCl₃, 400 MHz): δ 8.37-8.44 (2H, m), 7.92-7.79 (2H, m), 7.64-7.72 (3H, m), 7.45 (1H, d, J=8.0 Hz), 7.39 (2H, d, J=8.0 Hz), 7.16-7.23 (4H, m), 6.65-6.74 (3H, m), 3.82 (2H, s), 3.39 (2H, t, J=7.2 Hz), 2.89 (3H, s), 2.67 (2H, t, J=6.8 Hz), 2.34 (3H, s), 1.80 (2H, tt, J=7.0 Hz, J=7.0 Hz)

Mass spectrometric value (ESI-MS) 612 (M−1), 614 (M+1)

Compound 759 N-[4-Bromo-2-(4-fluoro-benzylidene-hydrazinocarbonyl)-phenyl]-4-{[3-(methyl-phenyl-amino)-propylamino]-methyl}-benzamide

The title compound 759 was produced in the same manner as in Example 8.

¹H-NMR (CDCl₃, 400 MHz): δ 8.37-8.46 (2H, m), 7.98 (2H, d, J=7.8 Hz), 7.81 (2H, bs), 7.66 (1H, s), 7.50 (1H, d, J=8.6 Hz), 7.43 (2H, d, J=8.1 Hz), 7.19-7.24 (2H, m), 7.11 (2H, dd, J=8.7 Hz, J=8.7 Hz), 6.66-6.75 (3H, m), 3.84 (2H, s), 3.41 (2H, t, J=7.2 Hz), 2.92 (3H, s), 2.69 (2H, t, J=7.0 Hz), 1.81 (2H, tt, J=7.0 Hz, J=7.0 Hz)

Mass spectrometric value (ESI-MS) 616 (M−1), 618 (M+1)

Compound 760 N-[4-Bromo-2-(3-fluoro-benzylidene-hydrazinocarbonyl)-phenyl]-4-{[3-(methyl-phenyl-amino)-propylamino]-methyl}-benzamide

The title compound 760 was produced in the same manner as in Example 8.

¹H-NMR (CDCl₃, 400 MHz): δ 8.45 (1H, bs), 8.34 (1H, d, J=8.5 Hz), 7.98 (2H, d, J=7.8 Hz), 7.34-7.67 (7H, m), 7.18-7.25 (2H, m), 7.11 (1H, ddd, J=1.7 Hz, J=7.6 Hz, J=7.6 Hz), 6.72 (2H, d, J=7.8 Hz), 6.68 (1H, dd, J=7.2 Hz, J=7.2 Hz), 3.84 (2H, s), 3.41 (2H, t, J=7.2 Hz), 2.91 (3H, s), 2.68 (2H, t, J=7.0 Hz), 1.80 (2H, tt, J=7.0 Hz, J=7.0 Hz)

Mass spectrometric value (ESI-MS) 614 (M−1), 618 (M+1)

Compound 761 N-[4-Bromo-2-(4-chloro-3-trifluoromethyl-benzylidene-hydrazinocarbonyl)-phenyl]-4-{[3-(methyl-phenyl-amino)-propylamino]-methyl}-benzamide

The title compound 761 was produced in the same manner as in Example 8.

¹H-NMR (CDCl₃, 400 MHz): δ 8.50 (1H, s), 8.27 (1H, d, J=8.0 Hz), 8.06 (1H, s), 7.99 (2H, d, J=7.6 Hz), 7.63 (1H, bs), 7.56 (1H, d, J=8.3 Hz), 7.45 (2H, d, J=8.1 Hz), 7.19-7.25 (2H, m), 6.65-6.75 (5H, m), 3.85 (2H, s), 3.41 (2H, t, J=7.1 Hz), 2.92 (3H, s), 2.69 (2H, t, J=7.0 Hz), 1.81 (2H, tt, J=7.0 Hz, J=7.0 Hz)

Mass spectrometric value (ESI-MS) 698, 700 (M−1), 702 (M+1)

Compound 762 N-[4-Bromo-2-(4-methoxy-benzylidene-hydrazinocarbonyl)-phenyl]-4-{[3-(methyl-phenyl-amino)-propylamino]-methyl}-benzamide

The title compound 762 was produced in the same manner as in Example 8.

¹H-NMR (CDCl₃, 400 MHz): δ 8.44 (1H, d, J=8.8 Hz), 8.37 (1H, s), 7.97 (2H, d, J=8.0 Hz), 7.65-7.77 (3H, m), 7.48 (1H, d, J=8.8 Hz), 7.40 (2H, d, J=8.0 Hz), 7.19-7.25 (3H, m), 6.90 (2H, d, J=8.8 Hz), 6.71 (2H, d, J=8.0 Hz), 6.68 (1H, dd, J=7.2 Hz, J=7.2 Hz), 3.81 (2H, s), 3.81 (3H, s), 3.40 (2H, t, J=7.1 Hz), 2.91 (3H, s), 2.67 (2H, t, J=7.0 Hz), 1.79 (2H, tt, J=7.0 Hz, J=7.0 Hz)

Mass spectrometric value (ESI-MS) 626 (M−1), 630 (M+1)

Compound 763 N-[4-Bromo-2-(3-methoxy-benzylidene-hydrazinocarbonyl)-phenyl]-4-{[3-(methyl-phenyl-amino)-propylamino]-methyl}-benzamide

The title compound 763 was produced in the same manner as in Example 8.

¹H-NMR (CDCl₃, 400 MHz): 3 8.44 (1H, d, J=9.0 Hz), 8.40 (1H, s), 7.97 (2H, d, J=7.8 Hz), 7.71 (1H, s), 7.18-7.54 (8H, m), 6.94-7.00 (1H, m), 6.71 (2H, d, J=8.0 Hz), 6.68 (1H, dd, J=7.2 Hz, J=7.2 Hz), 3.84 (3H, s), 3.82 (2H, s), 3.40 (2H, t, J=7.1 Hz), 2.91 (3H, s), 2.67 (2H, t, J=6.8 Hz), 1.80 (2H, tt, J=7.0 Hz, J=7.0 Hz),

Mass spectrometric value (ESI-MS) 626 (M−1), 630 (M+1)

Compound 764 N-[4-Bromo-2-(3,4-dimethyl-benzylidene-hydrazinocarbonyl)-phenyl]-4-[(2-ethylsulfanyl-ethylamino)-methyl]-benzamide

The title compound 764 was produced in the same manner as in Example 8.

¹H-NMR (CDCl₃, 400 MHz): δ 8.37-8.45 (2H, m), 7.98 (2H, d, J=7.8 Hz), 7.72 (1H, s), 7.60 (1H, s), 7.42-7.50 (4H, m), 7.07-7.20 (2H, m), 3.88 (2H, s), 2.83 (2H, t, J=6.2 Hz), 2.73 (2H, t, J=6.6 Hz), 2.51 (2H, q, J=7.3 Hz), 2.26 (3H, s), 2.25 (3H, s), 1.24 (3H, t, J=7.4 Hz)

Mass spectrometric value (ESI-MS) 565 (M−1)

Compound 765 N-[4-Bromo-2-(4-methyl-benzylidene-hydrazinocarbonyl)-phenyl]-4-[(2-ethylsulfanyl-ethylamino)-methyl]-benzamide

The title compound 765 was produced in the same manner as in Example 8.

¹H-NMR (CDCl₃, 400 MHz): δ 8.39-8.45 (2H, m), 7.84-8.02 (2H, m), 7.68 (2H, d, J=8.5 Hz), 7.42-7.50 (3H, m), 7.15-7.25 (3H, m), 3.88 (2H, s), 2.83 (2H, t, J=6.3 Hz), 2.73 (2H, t, J=6.3 Hz), 2.52 (2H, q, J=7.4 Hz), 2.36 (3H, s), 1.25 (3H, t, J=7.4 Hz)

Mass spectrometric value (ESI-MS) 551 (M−1)

Compound 766 N-[4-Bromo-2-(3-methyl-benzylidene-hydrazinocarbonyl)-phenyl]-4-[(2-ethylsulfanyl-ethylamino)-methyl]-benzamide

The title compound 766 was produced in the same manner as in Example 8.

¹H-NMR (CDCl₃, 400 MHz): δ 8.44 (1H, s), 8.37 (1H, d, J=8.8 Hz), 7.99 (2H, d, J=8.1 Hz), 7.68 (2H, s), 7.54 (1H, d, J=7.3 Hz), 7.42-7.50 (3H, m), 7.29 (1H, dd, J=7.6 Hz, J=7.6 Hz), 7.22 (1H, d, J=7.6 Hz), 3.87 (2H, s), 2.81 (2H, t, J=6.5 Hz), 2.72 (2H, t, J=6.2 Hz), 2.53 (2H, q, J=7.4 Hz), 2.37 (3H, s), 1.26 (3H, t, J=7.3 Hz)

Mass spectrometric value (ESI-MS) 551 (M−1)

Compound 767 N-[4-Bromo-2-(4-fluoro-benzylidene-hydrazinocarbonyl)-phenyl]-4-[(2-ethylsulfanyl-ethylamino)-methyl]-benzamide

The title compound 767 was produced in the same manner as in Example 8.

¹H-NMR (CDCl₃, 400 MHz): δ 8.46 (1H, s), 8.33 (1H, d, J=8.3 Hz), 7.98 (2H, d, J=7.8 Hz), 7.80 (2H, bs), 7.65 (1H, s), 7.45 (3H, d, J=8.0 Hz), 7.10 (2H, dd, J=8.5 Hz, J=8.5 Hz), 3.87 (2H, s), 2.82 (2H, t, J=6.3 Hz), 2.72 (2H, t, J=6.5 Hz), 2.53 (2H, q, J=7.4 Hz), 1.26 (3H, t, J=7.3 Hz)

Mass spectrometric value (ESI-MS) 557 (M−1)

Compound 768 N-[4-Bromo-2-(3-fluoro-benzylidene-hydrazinocarbonyl)-phenyl]-4-[(2-ethylsulfanyl-ethylamino)-methyl]-benzamide

The title compound 768 was produced in the same manner as in Example 8.

¹H-NMR (CDCl₃, 400 MHz): δ 8.46 (1H, bs), 8.34 (1H, d, J=7.8 Hz), 7.99 (2H, d, J=7.6 Hz), 7.66 (1H, bs), 7.34-7.60 (6H, m), 7.11 (1H, ddd, J=2.4 Hz, J=8.3 Hz, J=8.3 Hz), 3.89 (2H, s), 2.83 (2H, t, J=6.4 Hz), 2.73 (2H, t, J=6.3 Hz), 2.54 (2H, q, J=7.4 Hz), 1.26 (3H, t, J=7.2 Hz)

Mass spectrometric value (ESI-MS) 555 (M−1)

Compound 769 N-[4-Bromo-2-(4-chloro-3-trifluoromethyl-benzylidene-hydrazinocarbonyl)-phenyl]-4-[(2-ethylsulfanyl-ethylamino)-methyl]-benzamide

The title compound 769 was produced in the same manner as in Example 8.

¹H-NMR (CDCl₃, 400 MHz): δ 8.53 (1H, s), 8.27 (1H, d, J=6.8 Hz), 8.06 (1H, s), 7.99 (3H, d, J=7.8 Hz), 7.63 (1H, bs), 7.57 (1H, d, J=8.3 Hz), 7.40-7.50 (3H, m), 3.90 (2H, s), 2.84 (2H, t, J=6.2 Hz), 2.73 (2H, t, J=6.5 Hz), 2.54 (2H, q, J=7.4 Hz), 1.27 (3H, t, J=7.5 Hz)

Mass spectrometric value (ESI-MS) 643 (M−1)

Compound 770 N-[4-Bromo-2-(4-methoxy-benzylidene-hydrazinocarbonyl)-phenyl]-4-[(2-ethylsulfanyl-ethylamino)-methyl]-benzamide

The title compound 770 was produced in the same manner as in Example 8.

¹H-NMR (CDCl₃, 400 MHz): δ 8.37-8.45 (2H, m), 7.98 (2H, d, J=7.8 Hz), 7.68-7.74 (3H, m), 7.47 (1H, d, J=8.3 Hz), 7.42 (2H, d, J=8.0 Hz), 6.90 (2H, d, J=8.8 Hz), 3.86 (2H, s), 3.81 (3H, s), 2.81 (2H, t, J=6.5 Hz), 2.72 (2H, t, J=6.2 Hz), 2.52 (2H, q, J=7.4 Hz), 1.25 (3H, t, J=7.5 Hz)

Mass spectrometric value (ESI-MS) 569 (M−1)

Compound 771 N-[4-Bromo-2-(3-methoxy-benzylidene-hydrazinocarbonyl)-phenyl]-4-[(2-ethylsulfanyl-ethylamino)-methyl]-benzamide

The title compound 771 was produced in the same manner as in Example 8.

¹H-NMR (CDCl₃, 400 MHz): δ 8.45 (1H, s), 8.39 (1H, d, J=9.0 Hz), 7.97 (2H, d, J=7.8 Hz), 7.73 (1H, bs), 7.40-7.50 (3H, m), 7.34 (1H, s), 7.26-7.30 (2H, m), 6.90-7.00 (1H, m), 3.85 (2H, s), 3.83 (3H, s), 2.81 (2H, t, J=6.4 Hz), 2.71 (2H, t, J=6.2 Hz), 2.53 (2H, q, J=7.4 Hz), 1.25 (3H, t, J=7.4 Hz)

Mass spectrometric value (ESI-MS) 567 (M−1)

Compound 772 N-[4-Bromo-2-(3,4-dimethyl-benzylidene-hydrazinocarbonyl)-phenyl]-4-(4-pyridin-2-yl-piperazin-1-ylmethyl)-benzamide

The title compound 772 was produced in substantially the same manner as in Example 8.

¹H-NMR (CDCl₃, 400 MHz): δ 2.29 (3H, s), 2.30 (3H, s), 2.59 (4H, bs), 3.58 (4H, bs), 3.64 (2H, bs), 6.62 (2H, m), 7.18 (1H, d, J=7.8 Hz), 7.59 (7H, m), 8.00 (2H, d, J=8.1 Hz), 8.18 (1H, m), 8.31 (1H, s), 8.56 (1H, m), 10.08 (1H, bs), 11.68 (1H, s)

Mass spectrometric value (ESI-MS) 623 (M−1)

Compound 773 N-[4-Bromo-2-(4-methyl-benzylidene-hydrazinocarbonyl)-phenyl]-4-(4-pyridin-2-yl-piperazin-1-ylmethyl)-benzamide

The title compound 773 was produced in substantially the same manner as in Example 8.

¹H-NMR (CDCl₃, 400 MHz): δ 2.39 (3H, s), 2.59 (4H, bs), 3.58 (4H, bs), 3.64 (2H, bs), 6.63 (2H, m), 7.23 (2H, d, J=7.8 Hz), 7.59 (7H, m), 8.00 (2H, d, J=7.6 Hz), 8.18 (1H, m), 8.32 (1H, s), 8.60 (1H, d, J=8.8 Hz), 9.90 (1H, bs), 11.70 (1H, bs)

Mass spectrometric value (ESI-MS) 611 (M−1)

Compound 774 N-[4-Bromo-2-(4-fluoro-benzylidene-hydrazinocarbonyl)-phenyl]-4-(4-pyridin-2-yl-piperazin-1-ylmethyl)-benzamide

The title compound 774 was produced in substantially the same manner as in Example 8.

¹H-NMR (CDCl₃, 400 MHz): δ 2.59 (4H, bs), 3.59 (4H, bs), 3.65 (2H, bs), 6.63 (2H, m), 7.12 (2H, m), 7.64 (7H, m), 8.00 (2H, d, J=7.8 Hz), 8.18 (1H, m), 8.37 (1H, bs), 8.60 (1H, m), 10.20 (1H, bs), 11.70 (1H, bs)

Mass spectrometric value (ESI-MS) 613 (M−1)

Compound 775 N-[4-Bromo-2-(3-fluoro-benzylidene-hydrazinocarbonyl)-phenyl]-4-(4-pyridin-2-yl-piperazin-1-ylmethyl)-benzamide

The title compound 775 was produced in substantially the same manner as in Example 8.

¹H-NMR (CDCl₃, 400 MHz): δ 2.59 (4H, bs), 3.58 (4H, bs), 3.65 (2H, bs), 6.63 (2H, m), 7.14 (1H, m), 7.50 (8H, m), 8.00 (2H, d, J=7.8 Hz), 8.18 (1H, m), 8.40 (1H, s), 8.55 (1H, bs), 10.30 (1H, bs), 11.60 (1H, bs)

Mass spectrometric value (ESI-MS) 613 (M−1)

Compound 776 N-[4-Bromo-2-(4-chloro-3-trifluoromethyl-benzylidene-hydrazinocarbonyl)-phenyl]-4-(4-pyridin-2-yl-piperazin-1-ylmethyl)-benzamide

The title compound 776 was produced in substantially the same manner as in Example 8.

¹H-NMR (CDCl₃, 400 MHz): δ 2.60 (4H, bs), 3.58 (4H, bs), 3.65 (2H, bs), 6.63 (2H, m), 7.54 (6H, m), 8.02 (4H, m), 8.18 (1H, m), 8.47 (2H, bs), 10.45 (1H, bs), 11.50 (1H, bs)

Mass spectrometric value (ESI-MS) 697 (M−1)

Compound 777 N-[4-Bromo-2-(4-methoxy-benzylidene-hydrazinocarbonyl)-phenyl]-4-(4-pyridin-2-yl-piperazin-1-ylmethyl)-benzamide

The title compound 777 was produced in substantially the same manner as in Example 8.

¹H-NMR (CDCl₃, 400 MHz): δ 2.59 (4H, bs), 3.61 (6H, m), 3.84 (3H, s), 6.62 (2H, m), 6.93 (2H, d, J=8.8 Hz), 7.49 (4H, m), 7.72 (3H, m), 7.80 (2H, d, J=7.6 Hz), 8.18 (1H, m), 8.31 (1H, bs), 8.58 (1H, m), 9.99 (1H, bs), 11.69 (1H, bs)

Mass spectrometric value (ESI-MS) 625 (M−1)

Compound 778 N-[4-Bromo-2-(3-methoxy-benzylidene-hydrazinocarbonyl)-phenyl]-4-(4-pyridin-2-yl-piperazin-1-ylmethyl)-benzamide

The title compound 778 was produced in substantially the same manner as in Example 8.

¹H-NMR (CDCl₃, 400 MHz): δ 2.59 (4H, bs), 3.59 (6H, m), 3.86 (3H, s), 6.63 (2H, m), 6.98 (1H, m), 7.32 (3H, m), 7.54 (4H, m), 7.72 (1H, m), 8.00 (2H, d, J=7.3 Hz), 8.18 (1H, m), 8.34 (1H, bs), 8.60 (1H, d, J=8.8 Hz)

Mass spectrometric value (ESI-MS) 625 (M−1)

Compound 779 3-{[Bis-(2-hydroxy-propyl)-amino]-methyl}-N-[3-(4-chloro-3-trifluoromethyl-benzylidene-hydrazinocarbonyl)-thiophen-2-yl]-benzamide

The title compound 779 was produced in substantially the same manner as in Example 8.

¹H-NMR (CD₃OD, 400 MHz): δ 1.10 (6H, m), 2.51 (4H, m), 3.88 (4H, m), 7.03 (1H, d, J=6.1 Hz), 7.53 (2H, m), 7.68 (2H, d, J=8.0 Hz), 7.92 (1H, d, J=7.8 Hz), 8.06 (2H, m), 8.32 (1H, bs), 8.39 (1H, s)

Mass spectrometric value (ESI-MS) 595 (M−1)

Compound 780 3-{[Bis-(2-hydroxy-propyl)-amino]-methyl}-N-[3-(4-methoxy-benzylidene-hydrazinocarbonyl)-thiophen-2-yl]-benzamide

The title compound 780 was produced in substantially the same manner as in Example 8.

¹H-NMR (CD₃OD, 400 MHz): δ 1.10 (6H, m), 2.51 (4H, m), 3.88 (7H, m), 7.00 (3H, m), 7.53 (2H, m), 7.68 (1H, m), 7.80 (2H, d, J=8.3 Hz), 7.93 (1H, d, J=7.1 Hz), 8.06 (1H, m), 8.31 (1H, s)

Mass spectrometric value (ESI-MS) 523 (M−1)

Compound 781 2-{3-[3-(3,4-Dimethyl-benzylidene-hydrazinocarbonyl)-4-methyl-thiophen-2-ylcarbamoyl]-benzylsulfanyl}-ethanesulfonic acid

The title compound 781 was produced in substantially the same manner as in Example 8.

¹H-NMR (CD₃OD, 400 MHz): δ 2.30 (6H, m), 2.47 (3H, s), 2.79 (2H, m), 2.98 (2H, m), 3.85 (2H, bs), 6.71 (1H, m), 7.18 (1H, d, J=7.6 Hz), 7.20-8.00 (6H, m), 8.23 (1H, bs)

Mass spectrometric value (ESI-MS) 544 (M−1)

Compound 782 2-{3-[4-Methyl-3-(4-methyl-benzylidene-hydrazinocarbonyl)-thiophen-2-ylcarbamoyl]-benzylsulfanyl}-ethanesulfonic acid

The title compound 782 was produced in substantially the same manner as in Example 8.

¹H-NMR (CD₃OD, 400 MHz): δ 2.39 (3H, s), 2.47 (3H, s), 2.79 (2H, m), 2.99 (2H, m), 3.84 (2H, s), 6.72 (1H, m), 7.20-7.94 (8H, m), 8.26 (1H, bs)

Mass spectrometric value (ESI-MS) 530 (M−1)

Compound 783 2-{3-[3-(4-Fluoro-benzylidene-hydrazinocarbonyl)-4-methyl-thiophen-2-ylcarbamoyl]-benzylsulfanyl}-ethanesulfonic acid

The title compound 783 was produced in substantially the same manner as in Example 8.

¹H-NMR (CD₃OD, 400 MHz): δ 2.47 (3H, bs), 2.80 (2H, m), 2.99 (2H, m), 3.84 (2H, bs), 6.72 (1H, m), 7.14 (2H, m), 7.49 (1H, m), 7.61 (1H, m), 7.92 (4H, m), 8.29 (1H, bs)

Mass spectrometric value (ESI-MS) 534 (M−1)

Compound 784 2-{3-[3-(4-Chloro-3-trifluoromethyl-benzylidene-hydrazinocarbonyl)-4-methyl-thiophen-2-ylcarbamoyl]-benzylsulfanyl}-ethanesulfonic acid

The title compound 784 was produced in substantially the same manner as in Example 8.

¹H-NMR (CD₃OD, 400 MHz): δ 2.47 (3H, bs), 2.79 (2H, m), 2.98 (2H, m), 3.84 (2H, bs), 6.70 (1H, m), 7.40-8.02 (6H, m), 8.31 (2H, m)

Mass spectrometric value (ESI-MS) 618 (M−1)

Compound 785 2-{3-[3-(4-Methoxy-benzylidene-hydrazinocarbonyl)-4-methyl-thiophen-2-ylcarbamoyl]-benzylsulfanyl}-ethanesulfonic acid

The title compound 785 was produced in substantially the same manner as in Example 8.

¹H-NMR (CD₃OD, 400 MHz): δ 2.47 (3H, bs), 2.81 (2H, m), 2.98 (2H, m), 3.84 (5H, m), 6.71 (1H, m), 6.97 (2H, m), 7.44-7.98 (6H, m), 8.24 (1H, bs)

Mass spectrometric value (ESI-MS) 546 (M−1)

Compound 786 3-{[Bis-(2-hydroxy-ethyl)-amino]-methyl}-N-[3-(3,4-dimethyl-benzylidene-hydrazinocarbonyl)-4-methyl-thiophen-2-yl]-benzamide

The title compound 786 was produced in substantially the same manner as in Example 8.

¹H-NMR (CD₃OD, 400 MHz): δ 2.30 (6H, m), 2.50 (3H, s), 2.69 (4H, t, J=5.9 Hz), 3.63 (4H, t, J=5.5 Hz), 3.81 (2H, s), 6.69 (1H, m), 7.19 (1H, m), 7.51 (2H, m), 7.65 (2H, m), 7.87 (1H, m), 7.98 (1H, s), 8.22 (1H, s)

Mass spectrometric value (ESI-MS) 507 (M−1)

Compound 787 3-{[Bis-(2-hydroxy-ethyl)-amino]-methyl}-N-[4-methyl-3-(4-methyl-benzylidene-hydrazinocarbonyl)-thiophen-2-yl]-benzamide

The title compound 787 was produced in substantially the same manner as in Example 8.

¹H-NMR (CDCl₃, 400 MHz): δ 2.38 (3H, s), 2.57 (3H, s), 2.78 (4H, t, J=5.1 Hz), 3.74 (4H, t, J=5.1 Hz), 3.84 (2H, s), 6.50 (1H, s), 7.19 (2H, d, J=8.0 Hz), 7.45 (2H, m), 7.70 (2H, d, J=7.8 Hz), 8.00 (1H, m), 8.08 (1H, s), 8.25 (1H, s), 9.16 (1H, s)

Mass spectrometric value (ESI-MS) 493 (M−1)

Compound 788 3-{[Bis-(2-hydroxy-ethyl)-amino]-methyl}-N-[3-(4-fluoro-benzylidene-hydrazinocarbonyl)-4-methyl-thiophen-2-yl]-benzamide

The title compound 788 was produced in substantially the same manner as in Example 8.

¹H-NMR (CDCl₃, 400 MHz): δ 2.54 (3H, s), 2.79 (4H, t, J=5.2 Hz), 3.74 (4H, t, J=5.1 Hz), 3.83 (2H, s), 6.48 (1H, s), 7.04 (2H, m), 7.45 (2H, m), 7.80 (2H, m), 8.00 (1H, m), 8.13 (1H, s), 8.26 (1H, s), 9.28 (1H, s), 13.16 (1H, bs)

Mass spectrometric value (ESI-MS) 497 (M−1)

Compound 789 3-{[Bis-(2-hydroxy-ethyl)-amino]-methyl}-N-[3-(3-fluoro-benzylidene-hydrazinocarbonyl)-4-methyl-thiophen-2-yl]-benzamide

The title compound 789 was produced in substantially the same manner as in Example 8.

¹H-NMR (CDCl₃, 400 MHz): δ 2.56 (3H, s), 2.79 (4H, t, J=5.0 Hz), 3.75 (4H, m), 3.84 (2H, s), 6.47 (1H, s), 7.04 (1H, m), 7.17-7.70 (5H, m), 8.01 (1H, m), 8.16 (1H, s), 8.29 (1H, s), 9.35 (1H, s), 13.20 (1H, bs)

Mass spectrometric value (ESI-MS) 497 (M−1)

Compound 790 3-{[Bis-(2-hydroxy-ethyl)-amino]-methyl}-N-[3-(4-chloro-3-trifluoromethyl-benzylidene-hydrazinocarbonyl)-4-methyl-thiophen-2-yl]-benzamide

The title compound 790 was produced in substantially the same manner as in Example 8.

¹H-NMR (CD₃OD, 400 MHz): δ 2.50 (3H, s), 2.72 (4H, t, J=5.8 Hz), 3.65 (4H, t, J=5.8 Hz), 3.84 (2H, s), 6.71 (1H, d, J=1.0 Hz), 7.51 (1H, m), 7.67 (2H, m), 7.85 (1H, m), 8.00 (2H, m), 8.33 (2H, m)

Mass spectrometric value (ESI-MS) 581 (M−1)

Compound 791 3-{[Bis-(2-hydroxy-ethyl)-amino]-methyl}-N-[3-(4-methoxy-benzylidene-hydrazinocarbonyl)-4-methyl-thiophen-2-yl]-benzamide

The title compound 791 was produced in substantially the same manner as in Example 8.

¹H-NMR (CDCl₃, 400 MHz): δ 2.55 (3H, s), 2.79 (4H, t, J=5.2 Hz), 3.74 (4H, m), 3.85 (5H, m), 6.51 (1H, s), 6.92 (2H, m), 7.45 (2H, m), 7.67 (1H, m), 7.77 (1H, m), 8.01 (1H, m), 8.05 (1H, s), 8.26 (1H, s), 9.09 (1H, s), 13.27 (1H, bs)

Mass spectrometric value (ESI-MS) 509 (M−1)

Compound 792 3-{[Bis-(2-hydroxy-propyl)-amino]-methyl}-N-[3-(3,4-dimethyl-benzylidene-hydrazinocarbonyl)-benzo[b]thiophen-2-yl]-benzamide

The title compound 792 was produced in substantially the same manner as in Example 8.

¹H-NMR (CDCl₃, 400 MHz): δ 1.13 (3H, d, J=2.2 Hz), 1.15 (3H, d, J=2.2 Hz), 2.26 (6H, m), 2.51 (2H, d, J=6.1 Hz), 2.63 (2H, m), 3.65-4.05 (4H, m), 7.12 (1H, m), 7.30 (1H, m), 7.40-7.51 (4H, m), 7.67 (1H, m), 7.86 (2H, m), 8.03 (1H, m), 8.18 (1H, s), 8.25 (1H, d, J=5.6 Hz), 9.44 (1H, s), 13.13 (1H, m)

Mass spectrometric value (ESI-MS) 571 (M−1)

Compound 793 3-{[Bis-(2-hydroxy-propyl)-amino]-methyl}-N-[3-(4-methyl-benzylidene-hydrazinocarbonyl)-benzo[b]thiophen-2-yl]-benzamide

The title compound 793 was produced in substantially the same manner as in Example 8.

¹H-NMR (CDCl₃, 400 MHz): δ 1.13 (6H, m), 2.39 (3H, s), 2.51 (2H, d, J=6.1 Hz), 2.64 (2H, m), 3.65-4.05 (4H, m), 7.19 (2H, d, J=8.0 Hz), 7.32 (1H, m), 7.42-7.50 (3H, m), 7.75 (2H, m), 7.86 (2H, m), 8.04 (1H, m), 8.19 (1H, m), 8.28 (1H, d, J=6.1 Hz), 9.40 (1H, s), 13.14 (1H, bs)

Mass spectrometric value (ESI-MS) 557 (M−1)

Compound 794 3-{[Bis-(2-hydroxy-propyl)-amino]-methyl}-N-[3-(4-fluoro-benzylidene-hydrazinocarbonyl)-benzo[b]thiophen-2-yl]-benzamide

The title compound 794 was produced in substantially the same manner as in Example 8.

¹H-NMR (CDCl₃, 400 MHz): δ 1.13 (6H, m), 2.51 (2H, d, J=6.1 Hz), 2.65 (2H, m), 3.63-4.08 (4H, m), 7.07 (2H, m), 7.29 (1H, m), 7.36-7.50 (3H, m), 7.85 (4H, m), 8.03 (1H, m), 8.26 (2H, m), 9.50 (1H, d, J=4.4 Hz), 13.13 (1H, bs)

Mass spectrometric value (ESI-MS) 561 (M−1)

Compound 795 3-{[Bis-(2-hydroxy-propyl)-amino]-methyl}-N-[3-(3-fluoro-benzylidene-hydrazinocarbonyl)-benzo[b]thiophen-2-yl]-benzamide

The title compound 795 was produced in substantially the same manner as in Example 8.

¹H-NMR (CDCl₃, 400 MHz): δ 1.15 (6H, m), 2.53 (2H, m), 2.67 (2H, m), 3.61-4.14 (4H, m), 7.01 (1H, m), 7.11-7.30 (3H, m), 7.45 (3H, m), 7.62-7.90 (3H, m), 7.99 (1H, m), 8.23 (1H, d, J=12.7 Hz), 8.35 (1H, d, J=6.1 Hz), 9.82 (1H, d, J=13.9 Hz), 13.10 (1H, s)

Mass spectrometric value (ESI-MS) 561 (M−1)

Compound 796 3-{[Bis-(2-hydroxy-propyl)-amino]-methyl}-N-[3-(4-chloro-3-trifluoromethyl-benzylidene-hydrazinocarbonyl)-benzo[b]thiophen-2-yl]-benzamide

The title compound 796 was produced in substantially the same manner as in Example 8.

¹H-NMR (CDCl₃, 400 MHz): δ 1.14 (3H, d, J=6.1 Hz), 1.17 (3H, d, J=6.1 Hz), 2.50-2.80 (4H, m), 3.63-4.16 (4H, m), 7.06 (2H, m), 7.30 (1H, m), 7.44 (2H, m), 7.70 (1H, m), 7.80-8.07 (4H, m), 8.16 (1H, s), 8.53 (1H, s), 10.08 (1H, d, J=6.1 Hz), 13.10 (1H, d, J=1.0 Hz)

Mass spectrometric value (ESI-MS) 645 (M−1)

Compound 797 3-{[Bis-(2-hydroxy-propyl)-amino]-methyl}-N-[3-(4-methoxy-benzylidene-hydrazinocarbonyl)-benzo[b]thiophen-2-yl]-benzamide

The title compound 797 was produced in substantially the same manner as in Example 8.

¹H-NMR (CDCl₃, 400 MHz): δ 1.13 (6H, m), 2.51 (2H, d, J=6.1 Hz), 2.63 (2H, m), 3.64-4.06 (7H, m), 6.90 (2H, d, J=8.8 Hz), 7.31 (1H, m), 7.48 (3H, m), 7.83 (4H, m), 8.03 (1H, m), 8.18 (1H, m), 8.28 (1H, d, J=6.4 Hz), 9.38 (1H, s), 13.16 (1H, bs)

Mass spectrometric value (ESI-MS) 573 (M−1)

Compound 798 N-[3-(3,4-Dimethyl-benzylidene-hydrazinocarbonyl)-benzo[b]thiophen-2-yl]-3-(4-hydroxymethyl-piperidin-1-ylmethyl)-benzamide

The title compound 798 was produced in substantially the same manner as in Example 8.

¹H-NMR (CDCl₃, 400 MHz): δ 1.35 (2H, m), 1.51 (1H, m), 1.72 (2H, m), 2.05 (2H, m), 2.29 (3H, s), 2.30 (3H, s), 2.93 (2H, m), 3.50 (2H, d, J=6.1 Hz), 3.62 (2H, s), 7.18 (1H, d, J=7.8 Hz), 7.32 (1H, m), 7.47 (3H, m), 7.61 (1H, d, J=7.6 Hz), 7.66 (1H, s), 7.87 (2H, m), 7.97 (1H, m), 8.04 (1H, m), 8.17 (1H, m), 9.34 (1H, bs), 12.85 (1H, bs)

Mass spectrometric value (ESI-MS) 553 (M−1)

Compound 799 3-(4-Hydroxymethyl-piperidin-1-ylmethyl)-N-[3-(4-methyl-benzylidene-hydrazinocarbonyl)-benzo[b]thiophen-2-yl]-benzamide

The title compound 799 was produced in substantially the same manner as in Example 8.

¹H-NMR (CDCl₃, 400 MHz): δ 1.42 (2H, m), 1.52 (1H, m), 1.73 (2H, m), 2.12 (2H, m), 2.38 (3H, s), 3.00 (2H, m), 3.50 (2H, d, J=6.1 Hz), 3.70 (2H, s), 7.23 (2H, m), 7.32 (1H, m), 7.45 (2H, m), 7.64 (1H, d, J=7.8 Hz), 7.71 (2H, m), 8.86 (2H, m), 7.97 (1H, d, J=8.0 Hz), 8.03 (1H, m), 8.21 (1H, s), 9.40 (1H, bs), 12.84 (1H, bs)

Mass spectrometric value (ESI-MS) 539 (M−1)

Compound 800 N-[3-(4-Fluoro-benzylidene-hydrazinocarbonyl)-benzo[b]thiophen-2-yl]-3-(4-hydroxymethyl-piperidin-1-ylmethyl)-benzamide

The title compound 800 was produced in substantially the same manner as in Example 8.

¹H-NMR (CDCl₃, 400 MHz): δ 1.40-1.60 (3H, m), 1.73 (2H, m), 2.17 (2H, m), 3.05 (2H, m), 3.50 (2H, d, J=5.9 Hz), 3.75 (2H, s), 7.04 (1H, m), 7.11 (2H, m), 7.28 (1H, m), 7.37-7.50 (2H, m), 7.64 (1H, d, J=7.6 Hz), 7.83 (2H, m), 7.94 (1H, m), 8.01 (1H, s), 8.07 (1H, m), 8.26 (1H, s), 9.50 (1H, bs), 12.73 (1H, bs)

Mass spectrometric value (ESI-MS) 543 (M−1)

Compound 801 N-[3-(3-Fluoro-benzylidene-hydrazinocarbonyl)-benzo[b]thiophen-2-yl]-3-(4-hydroxymethyl-piperidin-1-ylmethyl)-benzamide

The title compound 801 was produced in substantially the same manner as in Example 8.

¹H-NMR (CDCl₃, 400 MHz): δ 1.40 (2H, m), 1.53 (1H, m), 1.72 (2H, m), 2.09 (2H, m), 2.96 (2H, m), 3.50 (2H, d, J=6.1 Hz), 3.66 (2H, s), 7.13 (1H, m), 7.31 (1H, dd, J=7.6 Hz, J=7.6 Hz), 7.35-7.66 (6H, m), 7.85 (2H, m), 7.94 (1H, d, J=7.8 Hz), 8.02 (1H, s), 8.23 (1H, s), 9.52 (1H, bs), 12.73 (1H, bs)

Mass spectrometric value (ESI-MS) 543 (M−1)

Compound 802 N-[3-(4-Chloro-3-trifluoromethyl-benzylidene-hydrazinocarbonyl)-benzo[b]thiophen-2-yl]-3-(4-hydroxymethyl-piperidin-1-ylmethyl)-benzamide

The title compound 802 was produced in substantially the same manner as in Example 8.

¹H-NMR (CDCl₃, 400 MHz): δ 1.40 (2H, m), 1.15 (1H, m), 1.72 (2H, m), 2.09 (2H, m), 2.95 (2H, m), 3.50 (2H, d, J=6.1 Hz), 3.65 (2H, s), 7.27 (1H, m), 7.40 (1H, dd, J=7.6 Hz, J=7.6 Hz), 7.47 (1H, dd, J=7.6 Hz, J=7.6 Hz), 7.55 (1H, d, J=8.0 Hz), 7.60 (1H, d, J=7.6 Hz), 7.82 (2H, m), 7.90 (1H, m), 7.95 (1H, d, J=8.0 Hz), 8.00 (1H, s), 8.06 (1H, s), 8.35 (1H, s), 9.69 (1H, bs), 12.63 (1H, bs)

Mass spectrometric value (ESI-MS) 627 (M−1)

Compound 803 3-(4-Hydroxymethyl-piperidin-1-ylmethyl)-N-[3-(4-methoxy-benzylidene-hydrazinocarbonyl)-benzo[b]thiophen-2-yl]-benzamide

The title compound 803 was produced in substantially the same manner as in Example 8.

¹H-NMR (CDCl₃, 400 MHz): δ 1.39 (2H, m), 1.52 (1H, m), 1.71 (2H, m), 2.07 (2H, m), 2.95 (2H, m), 3.49 (2H, d, J=6.1 Hz), 3.64 (2H, s), 3.83 (3H, s), 6.93 (2H, d, J=8.8 Hz), 7.29 (1H, m), 7.38-7.48 (2H, m), 7.60 (1H, d, J=7.6 Hz), 7.75 (1H, m), 7.84 (2H, dd, J=8.7 Hz, J=8.7 Hz), 7.95 (2H, m), 8.01 (1H, s), 8.20 (1H, s), 9.42 (1H, bs), 12.81 (1H, bs)

Mass spectrometric value (ESI-MS) 555 (M−1)

Example A Compound 804 3-{[Bis-(2-hydroxy-propyl)-amino]-methyl}-N-[3-(3,4-dimethyl-benzylidene-hydrazinocarbonyl)-5,6-dihydro-4H-cyclopenta[b]thiophen-2-yl]-benzamide

Ethyl-2-aminocyclopenta(B)thiophene-3-carboxylate (compound A) (1.0 g) was dissolved in anhydrous methylene chloride (20.0 ml). Subsequently, pyridine (760 μl) and 3-(chloromethyl)benzoyl chloride (compound B) (880 μl) were added to the solution at 0° C., and the mixture was stirred at 0° C. for one hr. After the completion of the reaction, distilled water was added thereto, and the mixture was subjected to separatory extraction with chloroform. The organic layer was washed with saturated brine, was dried over sodium sulfate, and was then concentrated to give 2-(3-chloromethyl-benzoylamino)-5,6-dihydro-4H-cyclopenta[b]thiophene-3-carboxylic acid ethyl ester as a useful intermediate (800 mg, crude yield 100%).

2-(3-Chloromethyl-benzoylamino)-5,6-dihydro-4H-cyclopenta[b]-thiophene-3-carboxylic acid ethyl ester (800 mg) produced by the above reaction was dissolved in anhydrous methylene chloride (10.0 ml). Triethylamine (420 μl) and diisopropanolamine (compound B′) (585 mg) were added to the solution at room temperature, and the mixture was stirred at room temperature for 15 hr. After the completion of the reaction, water was added thereto at room temperature, and the mixture was subjected to separatory extraction with chloroform. The organic layer was washed with saturated brine, was dried over sodium sulfate, and was then concentrated. The residue was purified by column chromatography eluted with a chloroform-methanol system to give 2-(3-{[bis-(2-hydroxy-propyl)-amino]-methyl}-benzoylamino)-5,6-dihydro-4H-cyclopenta[b]thiophene-3-carboxylic acid ethyl ester as a useful intermediate (616 mg, yield 61%).

2-(3-{[Bis-(2-hydroxy-propyl)-amino]-methyl}-benzoylamino)-5,6-dihydro-4H-cyclopenta[b]thiophene-3-carboxylic acid ethyl ester (616 mg) produced by the above reaction was dissolved in ethanol (10.0 ml). Hydrazine monohydrate (700 0) was added to the solution, and the mixture was stirred at room temperature for 15 hr. After the completion of the reaction, water was added thereto at room temperature, and the mixture was subjected to separatory extraction with chloroform. The organic layer was washed with saturated brine, was dried over sodium sulfate, and was then concentrated. The residue was purified by column chromatography eluted with a chloroform-methanol system to give 3-{[bis-(2-hydroxy-propyl)-amino]-methyl}-N-(3-hydrazinocarbonyl-5,6-dihydro-4H-cyclopenta[b]thiophen-2-yl)-benzamide as a hydrazine compound (372 mg, yield 60%).

3-{[Bis-(2-hydroxy-propyl)-amino]-methyl}-N-(3-hydrazino-carbonyl-5,6-dihydro-4H-cyclopenta[b]thiophen-2-yl)benzamide (60.0 mg) produced by the above reaction was dissolved in anhydrous toluene (1.0 ml). 3,4-Dimethylbenzaldehyde (compound C) (70.0 μl) was added to the solution at room temperature, and the mixture was heated under reflux with stirring for 15 hr. After the completion of the reaction, water was added thereto at room temperature, and the mixture was subjected to separatory extraction with chloroform. The organic layer was washed with saturated brine, was dried over sodium sulfate, and was then concentrated. The residue was purified by column chromatography eluted with a chloroform-methanol system to give the title compound 804 (70.0 mg, yield 100%).

¹H-NMR (CDCl₃, 400 MHz): δ 1.13 (6H, m), 2.28 (6H, m), 2.46-2.66 (6H, m), 2.92 (2H, m), 3.05 (2H, m), 3.58-4.05 (4H, m), 7.12 (1H, m), 7.46 (3H, m), 7.64 (1H, d, J=5.1 Hz), 8.00 (2H, m), 8.22 (1H, m), 8.95 (1H, s), 13.16 (1H, m)

Mass spectrometric value (ESI-MS) 561 (M−1)

Compound 805 3-{[Bis-(2-hydroxy-propyl)-amino]-methyl}-N-[3-(4-methyl-benzylidene-hydrazinocarbonyl)-5,6-dihydro-4H-cyclopenta[b]-thiophen-2-yl]-benzamide

The title compound 805 was produced in substantially the same manner as in Example A.

¹H-NMR (CDCl₃, 400 MHz): δ 1.13 (6H, m), 2.36 (3H, m), 2.49 (4H, m), 2.62 (2H, m), 2.89 (2H, m), 3.02 (2H, m), 3.60-4.06 (4H, m), 7.13 (2H, m), 7.44 (2H, m), 7.67 (2H, dd, J=8.2 Hz, J=2.6 Hz), 8.01 (2H, m), 8.23 (1H, m), 8.97 (1H, s), 13.16 (1H, m)

Mass spectrometric value (ESI-MS) 547 (M−1)

Compound 806 3-{[Bis-(2-hydroxy-propyl)-amino]-methyl}-N-[3-(3-fluoro-benzylidene-hydrazinocarbonyl)-5,6-dihydro-4H-cyclopenta[b]thiophen-2-yl]-benzamide

The title compound 806 was produced in substantially the same manner as in Example A.

¹H-NMR (CDCl₃, 400 MHz): δ 1.14 (6H, m), 2.50 (4H, m), 2.65 (2H, m), 2.89 (2H, m), 3.03 (2H, m), 3.68-4.10 (4H, m), 7.02 (1H, m), 7.27 (1H, m), 7.45 (3H, m), 7.67 (1H, m), 8.03 (1H, m), 8.15 (1H, d, J=2.7 Hz), 8.29 (1H, d, J=10.0 Hz), 9.11 (1H, s), 13.17 (1H, m)

Mass spectrometric value (ESI-MS) 551 (M−1)

Compound 807 3-{[Bis-(2-hydroxy-propyl)-amino]-methyl}-N-[3-(4-fluoro-benzylidene-hydrazinocarbonyl)-5,6-dihydro-4H-cyclopenta[b]thiophen-2-yl]-benzamide

The title compound 807 was produced in substantially the same manner as in Example A.

¹H-NMR (CDCl₃, 400 MHz): δ 1.12 (6H, m), 2.49 (4H, m), 2.64 (2H, m), 2.88 (2H, m), 3.02 (2H, m), 3.02-4.06 (4H, m), 7.01 (2H, m), 7.45 (2H, m), 7.79 (2H, m), 8.02 (1H, m), 8.10 (1H, s), 8.27 (1H, d, J=5.9 Hz), 9.04 (1H, s), 13.18 (1H, m)

Mass spectrometric value (ESI-MS) 551 (M−1)

Compound 808 3-{[Bis-(2-hydroxy-propyl)-amino]-methyl}-N-[3-(4-chloro-3-trifluoromethyl-benzylidene-hydrazinocarbonyl)-5,6-dihydro-4H-cyclopenta[b]thiophen-2-yl]-benzamide

The title compound 808 was produced in substantially the same manner as in Example A.

¹H-NMR (CDCl₃, 400 MHz): δ 1.12 (6H, m), 2.25-3.07 (10H, m), 3.58-4.10 (4H, m), 7.31 (1H, m), 7.46 (2H, m), 7.86 (1H, m), 7.98 (1H, s), 8.05 (1H, m), 8.33 (2H, m), 9.28 (1H, m), 13.18 (1H, m)

Mass spectrometric value (ESI-MS) 635 (M−1)

Compound 809 3-{[Bis-(2-hydroxy-propyl)-amino]-methyl}-N-[3-(4-methoxy-benzyl idene-hydrazinocarbonyl)-5,6-dihydro-4H-cyclopenta[b]thiophen-2-yl]-benzamide

The title compound 809 was produced in substantially the same manner as in Example A.

¹H-NMR (CDCl₃, 400 MHz): δ 1.13 (6H, m), 2.35-2.65 (6H, m), 2.91 (2H, m), 3.04 (2H, m), 3.59-4.04 (7H, m), 6.88 (2H, d, J=8.8 Hz), 7.46 (2H, m), 7.76 (2H, dd, J=9.1 Hz, J=2.1 Hz), 8.02 (2H, m), 8.24 (1H, m), 8.92 (1H, s), 13.20 (1H, m)

Mass spectrometric value (ESI-MS) 563 (M−1)

Example B Compound 810 3-[(2-Diethylamino-ethylamino)-methyl]-N-[3-(3,4-dimethyl-benzylidene-hydrazinocarbonyl)-5,6-dihydro-4H-cyclopenta[b]-thiophen-2-yl]-benzamide

Ethyl-2-aminocyclopenta (B)thiophene-3-carboxylate (compound A) (1.0 g) was dissolved in anhydrous methylene chloride (20.0 ml). Subsequently, pyridine (760 μl) and 3-(chloromethyl)benzoyl chloride (compound B) (880 μl) were added to the solution at 0° C., and the mixture was stirred at 0° C. for one hr. After the completion of the reaction, distilled water was added thereto, and the mixture was subjected to separatory extraction with chloroform. The organic layer was washed with saturated brine, was dried over sodium sulfate, and was then concentrated to give 2-(3-chloromethyl-benzoylamino)-5,6-dihydro-4H-cyclopenta[b]thiophene-3-carboxylic acid ethyl ester as a useful intermediate (800 mg, crude yield 100%).

2-(3-Chloromethyl-benzoylamino)-5,6-dihydro-4H-cyclopenta[b]-thiophene-3-carboxylic acid ethyl ester (800 mg) produced by the above reaction was dissolved in anhydrous methylene chloride (10.0 ml). Triethylamine (420 μl) and N,N-diethylethylenediamine (compound B′) (510 mg) were added to the solution at room temperature, and the mixture was stirred at room temperature for 15 hr. After the completion of the reaction, water was added thereto at room temperature, and the mixture was subjected to separatory extraction with chloroform. The organic layer was washed with saturated brine, was dried over sodium sulfate, and was then concentrated. The residue was purified by column chromatography eluted with a chloroform-methanol system to give 2-{3-[(2-diethylamino-ethylamino)-methyl]-benzoylamino}-5,6-dihydro-4H-cyclopenta[b]thiophene-3-carboxylic acid ethyl ester as a useful intermediate (671 mg, yield 68%).

2-{3-[(2-Di ethylamino-ethylamino)-methyl]-benzoylamino}-5,6-dihydro-4H-cyclopenta[b]thiophene-3-carboxylic acid ethyl ester (671 mg) produced by the above reaction was dissolved in ethanol (10.0 ml), hydrazine monohydrate (700 μl) was added to the solution, and the mixture was stirred at room temperature for 15 hr. After the completion of the reaction, water was added thereto at room temperature, and the mixture was subjected to separatory extraction with chloroform. The organic layer was washed with saturated brine, was dried over sodium sulfate, and was then concentrated. The residue was purified by column chromatography eluted with a chloroform-methanol system to give 3-[(2-diethylamino-ethylamino)-methyl-N-(3-hydrazinocarbonyl-5,6-dihydro-4H-cyclopenta[b]thiophen-2-yl)-benzamide (438 mg, yield 65%) as a hydrazine compound.

The hydrazine compound 3-[(2-diethylamino-ethylamino)-methyl-N-(3-hydrazinocarbonyl-5,6-dihydro-4H-cyclopenta[b]thiophen-2-yl)-benzamide (50 mg) produced by the above reaction was dissolved in anhydrous toluene (1.0 ml). 3,4-Dimethylbenzaldehyde (compound C) (70.0 μl) was added to the solution at room temperature, and the mixture was stirred at room temperature for 15 hr. After the completion of the reaction, the reaction product was purified by column chromatography eluted with a chloroform-methanol system to give the title compound 810 (43.0 mg, yield 66%).

¹H-NMR (CDCl₃, 400 MHz): δ 1.04 (6H, t, J=7.1 Hz), 2.28 (6H, s), 2.47-2.67 (8H, m), 2.74 (2H, m), 2.90 (2H, m), 3.05 (2H, m), 3.90 (2H, s), 7.14 (1H, d, J=7.8 Hz), 7.43 (2H, m), 7.57 (1H, d, J=7.8 Hz), 7.61 (1H, s), 7.94 (1H, d, J=7.8 Hz), 7.99 (2H, s), 8.96 (1H, bs), 12.95 (1H, bs)

Mass spectrometric value (ESI-MS) 544 (M−1)

Compound 811 3-[(2-Diethylamino-ethylamino)-methyl]-N-[3-(4-methyl-benzylidene-hydrazinocarbonyl)-5,6-dihydro-4H-cyclopenta[b]thiophen-2-yl]-benzamide

The title compound 811 was produced in substantially the same manner as in Example B.

¹H-NMR (CDCl₃, 400 MHz): δ 1.06 (6H, t, J=7.1 Hz), 2.38 (3H, s), 2.51-2.80 (10H, m), 2.93 (2H, m), 3.06 (2H, m), 3.91 (2H, s), 7.21 (2H, d, J=8.0 Hz), 7.45 (1H, dd, J=7.7 Hz, J=7.7 Hz), 7.58 (1H, d, J=7.6 Hz), 7.67 (2H, d, J=7.8 Hz), 7.95 (1H, d, J=7.8 Hz), 8.00 (1H, s), 8.04 (1H, s), 8.98 (1H, bs), 12.95 (1H, bs)

Mass spectrometric value (ESI-MS) 530 (M−1)

Compound 812 3-[(2-Diethylamino-ethylamino)-methyl]-N-[3-(3-fluoro-benzylidene-hydrazinocarbonyl)-5,6-dihydro-4H-cyclopenta[b]thiophen-2-yl]-benzamide

The title compound 812 was produced in substantially the same manner as in Example B.

¹H-NMR (CDCl₃, 400 MHz): δ 1.07 (6H, t, J=7.2 Hz), 2.51 (2H, m), 2.66 (4H, m), 2.73 (2H, m), 2.78 (2H, m), 2.89 (2H, m), 3.04 (2H, m), 3.90 (2H, s), 7.09 (1H, m), 7.35 (1H, m), 7.40-7.60 (4H, m), 7.92 (1H, d, J=7.8 Hz), 7.98 (1H, s), 8.09 (1H, s), 9.09 (1H, bs), 12.83 (1H, bs)

Mass spectrometric value (ESI-MS) 534 (M−1)

Compound 813 3-[(2-Diethylamino-ethylamino)-methyl]-N-[3-(4-fluoro-benzylidene-hydrazinocarbonyl)-5,6-dihydro-4H-cyclopenta[b]thiophen-2-yl]-benzamide

The title compound 813 was produced in substantially the same manner as in Example B.

¹H-NMR (CDCl₃, 400 MHz): δ 1.05 (6H, t, J=7.1 Hz), 2.49-2.70 (8H, m), 2.75 (2H, m), 2.91 (2H, t, J=7.3 Hz), 3.05 (2H, t, J=7.0 Hz), 3.90 (2H, s), 7.09 (2H, dd, J=8.6 Hz, J=8.6 Hz), 7.44 (1H, dd, J=7.7 Hz, J=7.7 Hz), 7.57 (1H, d, J=7.6 Hz), 7.76 (2H, m), 7.93 (1H, d, J=7.8 Hz), 7.99 (1H, s), 8.08 (1H, s), 9.02 (1H, bs), 12.88 (1H, bs)

Mass spectrometric value (ESI-MS) 534 (M−1)

Compound 814 N-[3-(4-Chloro-3-trifluoromethyl-benzylidene-hydrazinocarbonyl)-5,6-dihydro-4H-cyclopenta[b]thiophen-2-yl]-3-[(2-diethylamino-ethylamino)-methyl]-benzamide

The title compound 814 was produced in substantially the same manner as in Example B.

¹H-NMR (CDCl₃, 400 MHz): δ 1.03 (6H, t, J=7.2 Hz), 2.46-2.65 (8H, m), 2.71 (2H, m), 2.88 (2H, t, J=7.1 Hz), 3.03 (2H, t, J=6.8 Hz), 3.88 (2H, s), 7.45 (1H, dd, J=7.7 Hz, J=7.7 Hz), 7.54 (2H, m), 7.90 (2H, m), 7.98 (2H, m), 8.17 (1H, s), 9.13 (1H, bs), 12.78 (1H, bs)

Mass spectrometric value (ESI-MS) 618 (M−1)

Compound 815 3-[(2-Diethylamino-ethylamino)-methyl]-N-[3-(4-methoxy-benzylidene-hydrazinocarbonyl)-5,6-dihydro-4H-cyclopenta[b]thiophen-2-yl]-benzamide

The title compound 815 was produced in substantially the same manner as in Example B.

¹H-NMR (CDCl₃, 400 MHz): δ 1.03 (6H, t, J=7.1 Hz), 2.45-2.65 (8H, m), 2.71 (2H, m), 2.89 (2H, t, J=7.2 Hz), 3.03 (2H, t, J=7.1 Hz), 3.83 (3H, s), 3.89 (2H, s), 6.89 (2H, d, J=8.8 Hz), 7.44 (1H, dd, J=7.7 Hz, J=7.7 Hz), 7.56 (1H, d, J=7.6 Hz), 7.69 (2H, d, J=8.8 Hz), 7.93 (1H, d, J=8.1 Hz), 7.99 (2H, m), 8.93 (1H, bs), 12.94 (1H, bs)

Mass spectrometric value (ESI-MS) 546 (M−1)

Compound 816 N-[3-(3,4-Dimethyl-benzylidene-hydrazinocarbonyl)-5,6-dihydro-4H-cyclopenta[b]thiophen-2-yl]-3-(4-hydroxymethyl-piperidin-1-ylmethyl)-benzamide

The title compound 816 was produced in substantially the same manner as in Example A.

¹H-NMR (CDCl₃, 400 MHz): δ 1.38 (2H, m), 1.50 (1H, m), 1.73 (2H, d, J=12.0 Hz), 2.07 (2H, m), 2.30 (6H, s), 2.56 (2H, m), 2.94 (4H, m), 3.07 (2H, m), 3.50 (2H, d, J=6.1 Hz), 3.65 (2H, s), 7.17 (1H, d, J=7.8 Hz), 7.46 (2H, m), 7.60 (1H, d, J=7.8 Hz), 7.64 (1H, s), 7.97 (1H, d, J=7.6 Hz), 8.01 (2H, m), 8.96 (1H, s), 12.97 (1H, s)

Mass spectrometric value (ESI-MS) 543 (M−1)

Compound 817 3-(4-Hydroxymethyl-piperidin-1-ylmethyl)-N-[3-(4-methyl-benzylidene-hydrazinocarbonyl)-5,6-dihydro-4H-cyclopenta[b]thiophen-2-yl]-benzamide

The title compound 817 was produced in substantially the same manner as in Example A.

¹H-NMR (CDCl₃, 400 MHz): δ 1.39 (2H, m), 1.52 (1H, m), 1.72 (2H, d, J=11.5 Hz), 2.11 (2H, m), 2.39 (3H, s), 2.55 (2H, m), 2.90-3.02 (4H, m), 3.07 (2H, t, J=7.1 Hz), 3.49 (2H, d, J=6.1 Hz), 3.69 (2H, s), 7.21 (2H, d, J=8.1 Hz), 7.45 (1H, dd, J=7.5 Hz, J=7.5 Hz), 7.61 (1H, d, J=7.6 Hz), 7.67 (2H, d, J=8.0 Hz), 7.94-8.02 (2H, m), 8.05 (1H, s), 8.97 (1H, s), 12.95 (1H, s)

Mass spectrometric value (ESI-MS) 529 (M−1)

Compound 818 N-[3-(4-Fluoro-benzylidene-hydrazinocarbonyl)-5,6-dihydro-4H-cyclopenta[b]thiophen-2-yl]-3-(4-hydroxymethyl-piperidin-1-ylmethyl)-benzamide

The title compound 818 was produced in substantially the same manner as in Example A.

¹H-NMR (CDCl₃, 400 MHz): δ 1.35 (2H, m), 1.45-1.75 (3H, m), 2.03 (2H, m), 2.57 (2H, m), 2.94 (4H, m), 3.08 (2H, d, J=7.1 Hz), 3.50 (2H, d, J=6.1 Hz), 3.60 (2H, s), 7.12 (2H, dd, J=8.6 Hz, J=8.6 Hz), 7.45 (1H, dd, J=7.7 Hz, J=7.7 Hz), 7.58 (1H, d, J=7.6 Hz), 7.80 (2H, m), 7.95 (1H, d, J=7.8 Hz), 8.01 (1H, s), 8.09 (1H, s), 8.99 (1H, s), 12.90 (1H, s)

Mass spectrometric value (ESI-MS) 533 (M−1)

Compound 819 N-[3-(3-Fluoro-benzylidene-hydrazinocarbonyl)-5,6-dihydro-4H-cyclopenta[b]thiophen-2-yl]-3-(4-hydroxymethyl-piperidin-1-ylmethyl)-benzamide

The title compound 819 was produced in substantially the same manner as in Example A.

¹H-NMR (CDCl₃, 400 MHz): δ 1.36-1.62 (3H, m), 1.74 (2H, m), 2.14 (2H, m), 2.56 (2H, m), 2.90-3.14 (6H, m), 3.50 (2H, d, J=6.1 Hz), 3.72 (2H, s), 7.11 (1H, m), 7.38 (1H, m), 7.44-7.59 (3H, m), 7.62 (1H, m), 7.90-8.03 (2H, m), 8.10 (1H, s), 9.06 (1H, s), 12.88 (1H, s)

Mass spectrometric value (ESI-MS) 533 (M−1)

Compound 820 N-[3-(4-Chloro-3-trifluoromethyl-benzylidene-hydrazinocarbonyl)-5,6-dihydro-4H-cyclopenta[b]thiophen-2-yl]-3-(4-hydroxymethyl-piperidin-1-ylmethyl)-benzamide

The title compound 820 was produced in substantially the same manner as in Example A.

¹H-NMR (CDCl₃, 400 MHz): δ 1.30-1.77 (5H, m), 2.03 (2H, m), 2.58 (2H, m), 2.93 (4H, m), 3.08 (2H, d, J=7.1 Hz), 3.50 (2H, d, J=6.3 Hz), 3.60 (2H, s), 7.46 (1H, dd, J=7.6 Hz, J=7.6 Hz), 7.58 (2H, m), 7.90-8.06 (4H, m), 8.19 (1H, s), 9.09 (1H, s), 12.81 (1H, s)

Mass spectrometric value (ESI-MS) 617 (M−1)

Compound 821 3-(4-Hydroxymethyl-piperidin-1-ylmethyl)-N-[3-(4-methoxy-benzylidene-hydrazinocarbonyl)-5,6-dihydro-4H-cyclopenta[b]thiophen-2-yl]-benzamide

The title compound 821 was produced in substantially the same manner as in Example A.

¹H-NMR (CDCl₃, 400 MHz): δ 1.34 (2H, m), 1.50 (1H, m), 1.70 (2H, m), 2.02 (2H, m), 2.54 (2H, m), 2.91 (4H, m), 3.59 (2H, m), 3.49 (2H, d, J=6.3 Hz), 3.58 (2H, s), 3.85 (3H, s), 6.92 (2H, m), 7.44 (1H, dd, J=7.7 Hz, J=7.7 Hz), 7.57 (1H, d, J=7.6 Hz), 7.72 (2H, m), 7.94 (1H, d, J=7.8 Hz), 8.01 (2H, m), 8.92 (1H, s), 12.96 (1H, s)

Mass spectrometric value (ESI-MS) 545 (M−1)

Compound 822 3-Dimethylaminomethyl-N-[3-(3,4-dimethyl-benzylidene-hydrazinocarbonyl)-4-methyl-thiophen-2-yl]-benzamide

The title compound 822 was produced in substantially the same manner as in Example A.

¹H-NMR (CDCl₃, 400 MHz): δ 2.26 (6H, s), 2.29 (6H, s), 2.58 (3H, s), 3.53 (2H, s), 6.51 (1H, d, J=1.0 Hz), 7.17 (1H, d, J=7.8 Hz), 7.46 (2H, m), 7.57 (1H, d, J=7.6 Hz), 7.64 (1H, s), 7.95 (2H, m), 8.08 (1H, s), 9.11 (1H, s), 12.93 (1H, bs)

Mass spectrometric value (ESI-MS) 447 (M−1)

Compound 823 3-Dimethylaminomethyl-N-[4-methyl-3-(4-methyl-benzylidene-hydrazinocarbonyl)-thiophen-2-yl]-benzamide

The title compound 823 was produced in substantially the same manner as in Example A.

¹H-NMR (CDCl₃, 400 MHz): δ 2.26 (6H, s), 2.39 (3H, s), 2.58 (3H, s), 3.53 (2H, s), 6.52 (1H, d, J=1.0 Hz), 7.23 (2H, d, J=7.8 Hz), 7.46 (1H, dd, J=8.3 Hz, J=8.3 Hz), 7.57 (1H, d, J=7.8 Hz), 7.69 (2H, d, J=7.6 Hz), 7.95 (2H, m), 8.12 (1H, s), 9.12 (1H, s), 12.91 (1H, bs)

Mass spectrometric value (ESI-MS) 433 (M−1)

Compound 824 N-[3-(4-Chloro-3-trifluoromethyl-benzylidene-hydrazinocarbonyl)-4-methyl-thiophen-2-yl]-3-dimethylaminomethyl-benzamide

The title compound 824 was produced in substantially the same manner as in Example A.

¹H-NMR (CDCl₃, 400 MHz): δ 2.26 (6H, s), 2.52 (3H, s), 3.53 (2H, s), 6.49 (1H, s), 7.47 (1H, dd, J=7.7 Hz, J=7.7 Hz), 7.57 (2H, m), 7.94 (3H, m), 8.04 (1H, m), 8.27 (1H, s), 9.36 (1H, bs), 12.66 (1H, bs)

Mass spectrometric value (ESI-MS) 521 (M−1)

Compound 825 3-Dimethylaminomethyl-N-[3-(4-methoxy-benzylidene-hydrazinocarbonyl)-4-methyl-thiophen-2-yl]-benzamide

The title compound 825 was produced in substantially the same manner as in Example A.

¹H-NMR (CDCl₃, 400 MHz): δ 2.26 (6H, s), 2.57 (3H, s), 3.53 (2H, s), 3.85 (3H, s), 6.51 (1H, d, J=1.0 Hz), 6.93 (2H, m), 7.46 (1H, dd, J=7.6 Hz, J=7.6 Hz), 7.57 (1H, d, J=7.8 Hz), 7.74 (2H, d, J=8.8 Hz), 7.95 (2H, m), 8.09 (1H, s), 9.09 (1H, s), 12.93 (1H, bs)

Mass spectrometric value (ESI-MS) 449 (M−1)

Compound 826 N-[3-(3,4-Dimethyl-benzylidene-hydrazinocarbonyl)-4-methyl-thiophen-2-yl]-3-(4-pyrimidin-2-yl-piperazin-1-ylmethyl)-benzamide

The title compound 826 was produced in substantially the same manner as in Example A.

¹H-NMR (CDCl₃, 400 MHz): δ 2.29 (6H, s), 2.53 (4H, t, J=5.0 Hz), 2.59 (3H, s), 3.63 (2H, s), 3.84 (4H, t, J=5.0 Hz), 6.45 (1H, dd, J=4.6 Hz, J=4.6 Hz), 6.54 (1H, s), 7.17 (1H, d, J=7.6 Hz), 7.47 (2H, m), 7.60 (1H, d, J=7.6 Hz), 7.64 (1H, s), 7.96 (1H, d, J=7.8 Hz), 8.05 (1H, s), 8.07 (1H, s), 8.28 (2H, d, J=4.6 Hz), 9.07 (1H, s), 12.99 (1H, bs)

Mass spectrometric value (ESI-MS) 566 (M−1)

Compound 827 N-[4-Methyl-3-(4-methyl-benzylidene-hydrazinocarbonyl)-thiophen-2-yl]-3-(4-pyrimidin-2-yl-piperazin-1-ylmethyl)-benzamide

The title compound 827 was produced in substantially the same manner as in Example A.

¹H-NMR (CDCl₃, 400 MHz): δ 2.39 (3H, s), 2.53 (4H, t, J=5.0 Hz), 2.59 (3H, s), 3.64 (2H, s), 3.85 (4H, t, J=4.7 Hz), 6.46 (1H, dd, J=4.7 Hz, J=4.7 Hz), 6.53 (1H, s), 7.21 (2H, d, J=8.0 Hz), 7.47 (1H, dd, J=7.7 Hz, J=7.7 Hz), 7.60 (1H, d, J=7.6 Hz), 7.68 (2H, d, J=8.1 Hz), 7.96 (1H, d, J=7.8 Hz), 8.05 (1H, s), 8.11 (1H, s), 8.29 (2H, d, J=4.6 Hz), 9.09 (1H, s), 12.97 (1H, bs)

Mass spectrometric value (ESI-MS) 552 (M−1)

Compound 828 N-[3-(4-Fluoro-benzylidene-hydrazinocarbonyl)-4-methyl-thiophen-2-yl]-3-(4-pyrimidin-2-yl-piperazin-1-ylmethyl)-benzamide

The title compound 828 was produced in substantially the same manner as in Example A.

¹H-NMR (CDCl₃, 400 MHz): δ 2.54 (4H, t, J=5.0 Hz), 2.59 (3H, s), 3.64 (2H, s), 3.85 (4H, t, J=5.1 Hz), 6.46 (1H, dd, J=4.9 Hz, J=4.9 Hz), 6.54 (1H, s), 7.10 (2H, m), 7.46 (1H, dd, J=7.6 Hz, J=7.6 Hz), 7.60 (1H, d, J=7.6 Hz), 7.79 (2H, m), 7.95 (1H, d, J=7.8 Hz), 8.05 (1H, s), 8.15 (1H, s), 8.29 (2H, d, J=4.9 Hz), 9.12 (1H, s), 12.92 (1H, bs)

Mass spectrometric value (ESI-MS) 556 (M−1)

Compound 829 N-[3-(3-Fluoro-benzylidene-hydrazinocarbonyl)-4-methyl-thiophen-2-yl]-3-(4-pyrimidin-2-yl-piperazin-1-ylmethyl)-benzamide

The title compound 829 was produced in substantially the same manner as in Example A.

¹H-NMR (CDCl₃, 400 MHz): δ 2.53 (4H, t, J=5.0 Hz), 2.59 (3H, s), 3.64 (2H, s), 3.85 (4H, t, J=5.0 Hz), 6.46 (1H, dd, J=4.7 Hz, J=4.7 Hz), 6.55 (1H, s), 7.12 (1H, m), 7.38 (1H, m), 7.46-7.64 (4H, m), 7.95 (1H, m), 8.05 (1H, m), 8.17 (1H, s), 8.28 (2H, d, J=4.6 Hz), 9.17 (1H, s), 12.87 (1H, bs)

Mass spectrometric value (ESI-MS) 556 (M−1)

Compound 830 N-[3-(4-Chloro-3-trifluoromethyl-benzylidene-hydrazinocarbonyl)-4-methyl-thiophen-2-yl]-3-(4-pyrimidin-2-yl-piperazin-1-ylmethyl)-benzamide

The title compound 830 was produced in substantially the same manner as in Example A.

¹H-NMR (CDCl₃, 400 MHz): δ 2.53 (4H, t, J=5.0 Hz), 2.59 (3H, s), 3.65 (2H, s), 3.85 (4H, t, J=5.0 Hz), 6.46 (1H, dd, J=4.8 Hz, J=4.8 Hz), 6.55 (1H, s), 7.49 (1H, dd, J=7.7 Hz, J=7.7 Hz), 7.55 (1H, d, J=8.3 Hz), 7.61 (1H, d, J=7.6 Hz), 7.96 (2H, m), 8.05 (2H, m), 8.26 (1H, s), 8.28 (2H, d, J=4.6 Hz), 9.21 (1H, s), 12.84 (1H, bs)

Mass spectrometric value (ESI-MS) 640 (M−1)

Compound 831 N-[3-(4-Methoxy-benzylidene-hydrazinocarbonyl)-4-methyl-thiophen-2-yl]-3-(4-pyrimidin-2-yl-piperazin-1-ylmethyl)-benzamide

The title compound 831 was produced in substantially the same manner as in Example A.

¹H-NMR (CDCl₃, 400 MHz): δ 2.53 (4H, t, J=4.8 Hz), 2.60 (3H, s), 3.64 (2H, s), 3.84 (7H, m), 6.45 (1H, d, J=4.8 Hz), 6.55 (1H, s), 6.93 (2H, d, J=8.8 Hz), 7.47 (1H, dd, J=7.7 Hz, J=7.7 Hz), 7.61 (1H, d, J=7.6 Hz), 7.74 (2H, d, J=8.8 Hz), 7.97 (1H, d, J=7.8 Hz), 8.05 (1H, s), 8.08 (1H, s), 8.29 (2H, d, J=4.4 Hz), 9.02 (1H, s), 13.04 (1H, bs)

Mass spectrometric value (ESI-MS) 568 (M−1)

Compound 832 N-[3-(3,4-Dimethyl-benzylidene-hydrazinocarbonyl)-4-methyl-thiophen-2-yl]-3-(1,4-dioxa-8-aza-spiro[4,5]dec-8-ylmethyl)-benzamide

The title compound 832 was produced in substantially the same manner as in Example A.

¹H-NMR (CDCl₃, 400 MHz): δ 1.76 (4H, m), 2.31 (6H, s), 2.55 (4H, m), 2.62 (3H, s), 3.62 (2H, s), 3.94 (4H, s), 6.55 (1H, s), 7.26 (1H, m), 7.47 (2H, m), 7.53 (1H, m), 7.66 (1H, s), 7.95 (1H, d, J=7.8 Hz), 8.01 (1H, s), 8.07 (1H, s), 9.03 (1H, s), 13.03 (1H, bs)

Mass spectrometric value (ESI-MS) 545 (M−1)

Compound 833 3-(1,4-Dioxa-8-aza-spiro[4,5]dec-8-ylmethyl]-N-[4-methyl-3-(4-methyl-benzylidene-hydrazinocarbonyl)-thiophen-2-yl]-benzamide

The title compound 833 was produced in substantially the same manner as in Example A.

¹H-NMR (CDCl₃, 400 MHz): δ 1.76 (4H, t, J=5.5 Hz), 2.40 (3H, s), 2.55 (4H, m), 2.60 (3H, s), 3.62 (2H, s), 3.94 (4H, s), 6.54 (1H, s), 7.23 (2H, d, J=8.0 Hz), 7.45 (1H, dd, J=7.7 Hz, J=7.7 Hz), 7.58 (1H, d, J=7.8 Hz), 7.70 (2H, d, J=8.0 Hz), 7.93 (1H, d, J=7.8 Hz), 8.01 (1H, s), 8.11 (1H, s), 9.06 (1H, s), 12.97 (1H, bs)

Mass spectrometric value (ESI-MS) 531 (M−1)

Compound 834 3-(1,4-Dioxa-8-aza-spiro[4,5]dec-8-ylmethyl]-N-[3-(4-fluoro-benzylidene-hydrazinocarbonyl)-4-methyl-thiophen-2-yl]-benzamide

The title compound 834 was produced in substantially the same manner as in Example A.

¹H-NMR (CDCl₃, 400 MHz): δ 1.76 (4H, t, J=5.4 Hz), 2.56 (4H, m), 2.59 (3H, s), 3.62 (2H, s), 3.94 (4H, s), 6.55 (1H, s), 7.12 (2H, dd, J=8.6 Hz, J=8.6 Hz), 7.45 (1H, dd, J=7.7 Hz, J=7.7 Hz), 7.58 (1H, d, J=7.8 Hz), 7.81 (2H, m), 7.93 (1H, d, J=7.6 Hz), 8.01 (1H, s), 8.15 (1H, s), 9.10 (1H, s), 12.91 (1H, bs)

Mass spectrometric value (ESI-MS) 535 (M−1)

Compound 835 3-(1,4-Dioxa-8-aza-spiro[4,5]dec-8-ylmethyl]-N-[3-(3-fluoro-benzyl idene-hydrazinocarbonyl)-4-methyl-thiophen-2-yl]-benzamide

The title compound 835 was produced in substantially the same manner as in Example A.

¹H-NMR (CDCl₃, 400 MHz): δ 1.76 (4H, t, J=5.4 Hz), 2.55 (7H, m), 3.62 (2H, s), 3.94 (4H, s), 6.51 (1H, s), 7.11 (1H, m), 7.34-7.60 (5H, m), 7.91 (1H, d, J=7.6 Hz), 8.01 (1H, s), 8.18 (1H, s), 9.22 (1H, s), 12.78 (1H, bs)

Mass spectrometric value (ESI-MS) 535 (M−1)

Compound 836 N-[3-(4-Chloro-3-trifluoromethyl-benzylidene-hydrazinocarbonyl)-4-methyl-thiophen-2-yl]-3-(1,4-dioxa-8-aza-spiro[4,5]dec-8-ylmethyl]-benzamide

The title compound 836 was produced in substantially the same manner as in Example A.

¹H-NMR (CDCl₃, 400 MHz): δ 1.76 (4H, t, J=5.5 Hz), 2.57 (7H, m), 3.62 (2H, s), 3.94 (4H, s), 6.53 (1H, d, J=1.0 Hz), 7.46 (1H, dd, J=7.7 Hz, J=7.7 Hz), 7.57 (2H, m), 7.91 (1H, m), 7.96-8.02 (2H, m), 8.05 (1H, d, J=1.7 Hz), 8.27 (1H, s), 9.25 (1H, s), 12.76 (1H, bs)

Mass spectrometric value (ESI-MS) 619 (M−1)

Compound 837 3-(1,4-Dioxa-8-aza-spiro[4,5]dec-8-ylmethyl]-N-[3-(4-methoxy-benzylidene-hydrazinocarbonyl)-4-methyl-thiophen-2-yl]-benzamide

The title compound 837 was produced in substantially the same manner as in Example A.

¹H-NMR (CDCl₃, 400 MHz): δ 1.76 (4H, m), 2.56 (4H, m), 2.61 (3H, s), 3.63 (2H, s), 3.86 (3H, s), 3.94 (4H, s), 6.55 (1H, s), 6.95 (2H, m), 7.46 (1H, dd, J=7.6 Hz, J=7.6 Hz), 7.58 (1H, m), 7.76 (2H, d, J=8.5 Hz), 7.95 (1H, d, J=7.6 Hz), 8.01 (1H, s), 8.08 (1H, s), 9.00 (1H, s), 13.03 (1H, bs)

Mass spectrometric value (ESI-MS) 547 (M−1)

Compound 838 3-{[Bis-(2-diethylamino-ethyl)-amino]-methyl}-N-[3-(3,4-dimethyl-benzylidene-hydrazinocarbonyl)-4-methyl-thiophen-2-yl]-benzamide

The title compound 838 was produced in substantially the same manner as in Example B.

¹H-NMR (CDCl₃, 400 MHz): δ 0.98 (12H, t, J=7.1 Hz), 2.29 (6H, m), 2.43-2.66 (19H, m), 3.73 (2H, s), 6.52 (1H, d, J=1.0 Hz), 7.17 (1H, d, J=7.8 Hz), 7.44 (2H, m), 7.62 (2H, m), 7.92 (1H, d, J=7.8 Hz), 8.01 (1H, s), 8.09 (1H, s)

Mass spectrometric value (ESI-MS) 617 (M−1)

Compound 839 3-{[Bis-(2-diethylamino-ethyl)-amino]-methyl}-N-[4-methyl-3-(4-methyl-benzylidene-hydrazinocarbonyl)-thiophen-2-yl]-benzamide

The title compound 839 was produced in substantially the same manner as in Example B.

¹H-NMR (CDCl₃, 400 MHz): δ 0.98 (12H, t, J=7.1 Hz), 2.38 (3H, s), 2.45-2.65 (19H, m), 3.72 (2H, s), 6.51 (1H, d, J=1.2 Hz), 7.22 (2H, d, J=7.8 Hz), 7.43 (1H, m), 7.60 (1H, m), 7.68 (2H, d, J=7.8 Hz), 7.91 (1H, d, J=7.8 Hz), 8.00 (1H, s), 8.13 (1H, s)

Mass spectrometric value (ESI-MS) 603 (M−1)

Compound 840 3-{[Bis-(2-diethylamino-ethyl)-amino]-methyl}-N-[3-(4-fluoro-benzylidene-hydrazinocarbonyl)-4-methyl-thiophen-2-yl]-benzamide

The title compound 840 was produced in substantially the same manner as in Example B.

¹H-NMR (CDCl₃, 400 MHz): δ 0.98 (12H, t, J=7.1 Hz), 2.43-2.66 (19H, m), 3.72 (2H, s), 6.50 (1H, d, J=1.0 Hz), 7.10 (2H, dd, J=8.5 Hz, J=8.5 Hz), 7.44 (1H, m), 7.62 (1H, d, J=7.6 Hz), 7.79 (2H, m), 7.89 (1H, d, J=7.8 Hz), 8.00 (1H, s), 8.18 (1H, s)

Mass spectrometric value (ESI-MS) 607 (M−1)

Compound 841 3-{[Bis-(2-diethylamino-ethyl)-amino]-methyl}-N-[3-(3-fluoro-benzyl idene-hydrazinocarbonyl)-4-methyl-thiophen-2-yl]-benzamide

The title compound 841 was produced in substantially the same manner as in Example B.

¹H-NMR (CDCl₃, 400 MHz): δ 0.98 (12H, t, J=7.1 Hz), 2.44-2.64 (19H, m), 3.73 (2H, s), 6.51 (1H, s), 7.11 (1H, s), 7.34-7.64 (5H, m), 7.90 (1H, d, J=7.8 Hz), 8.01 (1H, s), 8.19 (1H, s)

Mass spectrometric value (ESI-MS) 607 (M−1)

Compound 842 3-{[Bis-(2-diethylamino-ethyl)-amino]-methyl}-N-[3-(4-chloro-3-trifluoromethyl-benzylidene-hydrazinocarbonyl)-4-methyl-thiophen-2-yl]-benzamide

The title compound 842 was produced in substantially the same manner as in Example B.

¹H-NMR (CDCl₃, 400 MHz): δ 0.97 (12H, m), 2.42-2.64 (19H, m), 3.72 (2H, m), 6.47 (1H, d, J=1.0 Hz), 7.30-7.68 (4H, m), 7.77-8.05 (3H, m), 8.27 (1H, s)

Mass spectrometric value (ESI-MS) 691 (M−1)

Compound 843 3-{[Bis-(2-diethylamino-ethyl)-amino]-methyl}-N-[3-(4-methoxy-benzylidene-hydrazinocarbonyl)-4-methyl-thiophen-2-yl]-benzamide

The title compound 843 was produced in substantially the same manner as in Example B.

¹H-NMR (CDCl₃, 400 MHz): δ 0.98 (12H, t, J=7.2 Hz), 2.45-2.66 (19H, m), 3.72 (2H, s), 3.85 (3H, s), 6.52 (1H, d, J=1.0 Hz), 6.93 (2H, d, J=8.8 Hz), 7.44 (1H, m), 7.62 (1H, d, J=7.8 Hz), 7.74 (2H, d, J=8.6 Hz), 7.92 (1H, d, J=7.8 Hz), 8.01 (1H, s), 8.10 (1H, s)

Mass spectrometric value (ESI-MS) 619 (M−1)

Compound 844 3-{[Bis-(2-hydroxy-propyl)-amino]-methyl}-N-[3-(3,4-dimethyl-benzylidene-hydrazinocarbonyl)-4,5-dimethyl-thiophen-2-yl]-benzamide

The title compound 844 was produced in substantially the same manner as in Example B.

¹H-NMR (CDCl₃, 400 MHz): δ 1.12 (6H, m), 2.26-2.64 (16H, m), 3.62-4.05 (4H, m), 7.13 (1H, m), 7.40-7.56 (3H, m), 7.65 (1H, m), 7.99 (1H, m), 8.04 (1H, s), 8.19 (1H, s), 9.10 (1H, s), 13.02 (1H, bs)

Mass spectrometric value (ESI-MS) 549 (M−1)

Compound 845 3-{[Bis-(2-hydroxy-propyl)-amino]-methyl}-N-[4,5-dimethyl-3-(4-methyl-benzylidene-hydrazinocarbonyl)-thiophen-2-yl]-benzamide

The title compound 845 was produced in substantially the same manner as in Example B.

¹H-NMR (CDCl₃, 400 MHz): δ 1.11 (6H, m), 2.28-2.64 (13H, m), 3.60-4.04 (4H, m), 7.21 (2H, m), 7.43 (2H, m), 7.73 (2H, m), 7.99 (1H, m), 8.07 (1H, s), 8.21 (1H, s), 9.09 (1H, bs), 13.01 (1H, bs)

Mass spectrometric value (ESI-MS) 535 (M−1)

Compound 846 3-{[Bis-(2-hydroxy-propyl)-amino]-methyl}-N-[3-(4-fluoro-benzylidene-hydrazinocarbonyl)-4,5-dimethyl-thiophen-2-yl]-benzamide

The title compound 846 was produced in substantially the same manner as in Example B.

¹H-NMR (CDCl₃, 400 MHz): δ 1.11 (6H, m), 2.24-2.52 (8H, m), 2.63 (2H, m), 3.60-4.06 (4H, m), 7.04 (2H, m), 7.43 (2H, m), 7.83 (2H, m), 7.99 (1H, m), 8.13 (1H, s), 8.24 (1H, m), 9.24 (1H, s), 12.98 (1H, bs)

Mass spectrometric value (ESI-MS) 539 (M−1)

Compound 847 3-{[Bis-(2-hydroxy-propyl)-amino]-methyl}-N-[3-(4-chloro-3-trifluoromethyl-benzylidene-hydrazinocarbonyl)-4,5-dimethyl-thiophen-2-yl]-benzamide

The title compound 847 was produced in substantially the same manner as in Example B.

¹H-NMR (CDCl₃, 400 MHz): δ 1.11 (6H, m), 2.19 (3H, m), 2.28 (3H, m), 2.52 (2H, m), 2.67 (2H, m), 3.60-4.10 (4H, m), 7.33 (1H, d, J=8.3 Hz), 7.38-7.50 (2H, m), 7.86 (1H, m), 7.98-8.10 (2H, m), 8.28 (1H, s), 8.36 (1H, s), 9.57 (1H, s), 13.03 (1H, s)

Mass spectrometric value (ESI-MS) 623 (M−1)

Compound 848 3-{[Bis-(2-hydroxy-propyl)-amino]-methyl}-N-[3-(4-methoxy-benzylidene-hydrazinocarbonyl)-4,5-dimethyl-thiophen-2-yl]-benzamide

The title compound 848 was produced in substantially the same manner as in Example B.

¹H-NMR (CDCl₃, 400 MHz): δ 1.11 (6H, m), 2.24-2.64 (10H, m), 3.60-4.04 (7H, m), 6.91 (2H, m), 7.43 (2H, m), 7.79 (2H, m), 8.02 (2H, m), 8.23 (1H, s), 9.04 (1H, s), 13.02 (1H, bs)

Mass spectrometric value (ESI-MS) 551 (M−1)

Compound 849 3-{[Bis-(2-diethylamino-ethyl)-amino]-methyl}-N-[3-(4-chloro-3-trifluoromethyl-benzylidene-hydrazinocarbonyl)-4,5,6,7-tetrahydro-benzo[b]thiophen-2-yl]-benzamide

The title compound 849 was produced in substantially the same manner as in Example B.

¹H-NMR (CDCl₃, 400 MHz): δ 0.98 (12H, t, J=7.1 Hz), 1.91 (4H, m), 2.48 (8H, m), 2.58 (8H, m), 2.76 (2H, m), 2.87 (2H, m), 3.73 (2H, s), 7.44 (1H, dd, J=7.7 Hz, J=7.7 Hz), 7.57 (1H, d, J=8.3 Hz), 7.62 (1H, d, J=7.6 Hz), 7.90 (1H, d, J=8.1 Hz), 7.97 (1H, dd, J=8.3 Hz, J=2.0 Hz), 8.00 (1H, s), 8.04 (1H, d, J=1.7 Hz), 8.22 (1H, s)

Mass spectrometric value (ESI-MS) 731 (M−1)

Compound 850 3-{[Bis-(2-diethylamino-ethyl)-amino]-methyl}-N-[3-(4-methoxy-benzylidene-hydrazinocarbonyl)-4,5,6,7-tetrahydro-benzo[b]-thiophen-2-yl]-benzamide

The title compound 850 was produced in substantially the same manner as in Example B.

¹H-NMR (CDCl₃, 400 MHz): δ 0.98 (12H, t, J=7.2 Hz), 1.92 (4H, m), 2.49 (8H, m), 2.58 (8H, m), 2.76 (2H, m), 2.89 (2H, m), 3.72 (2H, s), 3.88 (3H, s), 6.97 (2H, m), 7.27-7.46 (3H, m), 7.61 (1H, d, J=7.8 Hz), 7.92 (1H, d, J=7.3 Hz), 8.00 (1H, s), 8.10 (1H, s)

Mass spectrometric value (ESI-MS) 659 (M−1)

Example C Compound 851 3-{[Bis-(2-hydroxy-propyl)-amino]-methyl}-N-[3-(4-chloro-3-trifluoromethyl-benzylidene-hydrazinocarbonyl)-4-methyl-thiophen-2-yl]-benzamide; hydrochloride

Diethyl ether (200 μl) was added to compound 591: 3-{[bis-(2-hydroxy-propyl)-amino]-methyl}-N-[3-(4-chloro-3-trifluoromethyl-benzylidene-hydrazinocarbonyl)-4-methyl-thiophen-2-yl]-benzamide (30 mg) produced by the process described in Example 8 at room temperature. Further, a few drops of 10% hydrochloric acid-methanol were added thereto, and the mixture was stirred for a few minutes. The reaction solution was then filtered through Kiriyama Rohto, and the crystals were washed with diethyl ether to give the title compound 851 (25 mg, yield 80%).

¹H-NMR (CDCl₃, 400 MHz): δ 1.14-1.27 (6H, m), 2.56 (3H, s), 2.90 (4H, m), 4.22 (4H, m), 6.53 (1H, m), 7.53 (2H, m), 7.70 (1H, m), 7.95 (1H, m), 8.03 (1H, d, J=8.0 Hz), 8.07 (1H, s), 8.20 (1H, d, J=7.3 Hz), 8.36 (1H, m)

Mass spectrometric value (ESI-MS) 609 (M−1)

Compound 852 3-{[Bis-(2-hydroxy-propyl)-amino]-methyl}-N-[3-(4-methoxy-benzylidene-hydrazinocarbonyl)-4-methyl-thiophen-2-yl]-benzamide; hydrochloride

The title compound 852 was produced in substantially the same manner as in Example C.

¹H-NMR (CD₃OD, 400 MHz): δ 1.22 (6H, d, J=6.1 Hz), 2.53 (3H, s), 3.30 (4H, m), 3.85 (3H, s), 4.20 (4H, m), 6.73 (1H, d, J=1.0 Hz), 6.99 (2H, d, J=8.5 Hz), 7.60-7.85 (4H, m), 8.00-8.29 (3H, m)

Mass spectrometric value (ESI-MS) 538 (M−1)

Example D Compound 853 3-{[Bis-(2-hydroxy-propyl)-amino]-methyl}-N-[2-(4-chloro-3-trifluoromethyl-benzylidene-hydrazinocarbonyl)-4-fluoro-phenyl]-benzamide; hydrochloride

Diethyl ether (200 μl) was added to compound 857: 3-{[bis-(2-hydroxy-propyl)-amino]-methyl}-N-[2-(4-chloro-3-trifluoromethyl-benzylidene-hydrazinocarbonyl)-4-fluoro-phenyl]-benzamide (30 mg) produced by the process described in Example A at room temperature, a few drops of 10% hydrochloric acid-methanol were further added thereto, and the mixture was stirred for a few minutes. The reaction solution was then filtered through Kiriyama Rohto, and the crystals were washed with diethyl ether to give the title compound 853 (25 mg, yield 80%).

¹H-NMR (CD₃OD, 400 MHz): δ 1.15-1.32 (6H, m), 3.00-3.40 (4H, m), 4.10-4.86 (4H, m), 7.44 (1H, m), 7.68-7.85 (4H, m), 8.03 (1H, d, J=7.8 Hz), 8.14 (2H, m), 8.36 (1H, m), 8.41 (1H, s), 8.62 (1H, m)

Mass spectrometric value (ESI-MS) 608 (M−1)

Compound 854 3-{[Bis-(2-hydroxy-propyl)-amino]-methyl}-N-[4-fluoro-2-(4-methoxy-benzylidene-hydrazinocarbonyl)-phenyl]-benzamide; hydrochloride

The title compound 854 was produced in substantially the same manner as in Example D.

¹H-NMR (CD₃OD, 400 MHz): δ 1.18 (6H, m), 3.30 (4H, m), 3.85 (3H, s), 4.00-4.30 (4H, m), 6.98 (2H, d, J=8.5 Hz), 7.35 (1H, m), 7.65-7.83 (5H, m), 8.00-8.17 (2H, m), 8.31 (1H, s), 8.70 (1H, m)

Mass spectrometric value (ESI-MS) 536 (M−1)

Example E Compound 855 3-{[Bis-(2-diethylamino-ethyl)-amino]-methyl}-N-[3-(4-chloro-3-trifluoromethyl-benzylidene-hydrazinocarbonyl)-4,5,6,7-tetrahydro-benzo[b]thiophen-2-yl]-benzamide; hydrochloride

Diethyl ether (200 μl) was added to compound 849: 3-{[bis-(2-diethylamino-ethyl)-amino]-methyl}-N-[3-(4-chloro-3-trifluoromethyl-benzylidene-hydrazinocarbonyl)-4,5,6,7-tetrahydro-benzo[b]thiophen-2-yl]-benzamide (30 mg) produced by the process described in Example B at room temperature, a few drops of 10% hydrochloric acid-methanol were further added thereto, and the mixture was stirred for a few minutes. The reaction solution was then filtered through Kiriyama Rohto, and the crystals were washed with diethyl ether to give the title compound 855 (25 mg, yield 80%).

¹H-NMR (CD₃OD, 400 MHz): δ 1.28 (12H, m), 1.91 (4H, m), 2.77 (2H, m), 2.87 (2H, m), 3.04 (4H, m), 3.18 (8H, m), 3.40 (4H, m), 3.92 (2H, s), 7.62 (1H, m), 7.70 (1H, m), 7.77 (1H, m), 7.95 (1H, m), 8.01 (2H, m), 8.32 (2H, m)

Mass spectrometric value (ESI-MS) 732 (M−1)

Compound 856 3-{[Bis-(2-diethylamino-ethyl)-amino]-methyl}-N-[3-(4-methoxy-benzylidene-hydrazinocarbonyl)-4,5,6,7-tetrahydro-benzo[b]thiophen-2-yl]-benzamide; hydrochloride

The title compound 856 was produced in substantially the same manner as in Example E.

¹H-NMR (CD₃OD, 400 MHz): δ 1.29 (12H, m), 1.89 (4H, m), 2.70-2.92 (4H, m), 3.00-3.28 (12H, m), 3.43 (4H, m), 3.87 (3H, s), 3.97 (2H, s), 7.20 (1H, m), 7.30-7.40 (2H, m), 7.52 (1H, m), 7.63 (1H, m), 7.77 (1H, m), 7.98 (1H, m), 8.04 (1H, s), 8.27 (1H, s)

Mass spectrometric value (ESI-MS) 660 (M−1)

Compound 857 3-{[Bis-(2-hydroxy-propyl)-amino]-methyl}-N-[2-(4-chloro-3-trifluoromethyl-benzylidene-hydrazinocarbonyl)-4-fluoro-phenyl]-benzamide

The title compound 857 was produced in substantially the same manner as in Example A.

¹H-NMR (CD₃OD, 400 MHz): δ 1.08 (6H, m), 2.43-2.60 (4H, m), 3.60-3.95 (4H, m), 7.40 (1H, m), 7.50 (1H, m), 7.60 (1H, m), 7.69 (2H, d, J=7.6 Hz), 7.85 (1H, m), 8.07 (2H, m), 8.34 (1H, m), 8.38 (1H, s), 8.65 (1H, m),

Mass spectrometric value (ESI-MS) 608 (M−1)

Example F Compound 858 3-{[(2-Diethylamino-ethyl)-methyl-amino]-methyl}-N-[2-(3,4-dimethyl-benzylidene-hydrazinocarbonyl)-4-piperidin-1-ylphenyl]-benzamide

5-Chloro-2-nitro-benzoic acid (compound A′) (5.0 g) was dissolved in methanol (150 ml). Thionyl chloride (9.5 ml) was added to the solution at 0° C., and the mixture was heated under reflux with stirring for 15 hr. After the completion of the reaction, distilled water was added thereto at 0° C., and the mixture was subjected to separatory extraction with chloroform. The organic layer was washed with distilled water and saturated brine, was dried over sodium sulfate, and was then concentrated to give 5-chloro-2-nitro-benzoic acid methyl ester as a useful intermediate (12.9 g, yield 92%).

5-Chloro-2-nitro-benzoic acid methyl ester (2.2 g) produced by the above reaction was dissolved in N,N-dimethylformamide (20 ml). Piperidine (compound D) (1.5 g) and potassium carbonate (1.5 g) were added to the solution at room temperature, and the mixture was stirred at 75° C. for 15 hr. After the completion of the reaction, distilled water was added thereto at room temperature, and the mixture was subjected to separatory extraction with chloroform. The organic layer was washed with distilled water and saturated brine, was dried over sodium sulfate, and was then concentrated to give 2-nitro-5-piperidin-1-yl-benzoic acid methyl ester as a useful intermediate (1.86 g, crude yield 69%).

2-Nitro-5-piperidin-1-yl-benzoic acid methyl ester (4.8 g) produced by the above reaction was dissolved in ethanol (5.0 ml), and 10% palladium-carbon (500 mg) was added to the solution. The air in the reaction system was then replaced by hydrogen, and the reaction solution was stirred at room temperature for 15 hr. After the completion of the reaction, the atmosphere in the reaction system was replaced by nitrogen, followed by filtration through Celite. The filterate was concentrated, and the residue was purified by column chromatography using a hexane-acetone system to give 2-amino-5-piperidin-1-yl-benzoic acid methyl ester (compound A) as a useful intermediate (3.7 g, yield 87%).

2-Amino-5-piperidin-1-yl-benzoic acid methyl ester (compound A) (2.1 g) produced by the above reaction was dissolved in anhydrous methylene chloride (20.0 ml). Subsequently, pyridine (900 μl) and 3-(chloromethyl)benzoyl chloride (compound B) (740 μl) were added to the solution at 0° C., and the mixture was stirred at 0° C. for one hr. After the completion of the reaction, distilled water was added thereto, and the mixture was subjected to separatory extraction with chloroform. The organic layer was washed with saturated brine, was dried over sodium sulfate and was then concentrated. The residue was purified by column chromatography using a chloroform-acetone system to give 2-(3-chloromethyl-benzoylamino)-5-piperidin-1-yl-benzoic acid methyl ester as a useful intermediate (1.8 g, yield 50%).

2-(3-Chloromethyl-benzoylamino)-5-piperidin-1-yl-benzoic acid methyl ester (500 mg) produced by the above reaction was dissolved in anhydrous methylene chloride (5.0 ml). Triethylamine (400 μl) and N,N-diethyl-N-methylethylenediamine (compound B′) (325 mg) were added to the solution at room temperature, and the mixture was stirred at room temperature for 15 hr. After the completion of the reaction, water was added thereto at room temperature, and the mixture was subjected to separatory extraction with chloroform. The organic layer was washed with saturated brine, was dried over sodium sulfate, and was then concentrated. The residue was purified by column chromatography eluted with a chloroform-methanol system to give 2-(3-{[(2-diethylamino-ethyl)-methyl-amino]-methyl}-benzoylamino)-5-piperidin-1-yl-benzoic acid methyl ester as a useful intermediate (612 mg, yield 98%).

2-(3-{[(2-Diethylamino-ethyl)-methyl-amino]-methyl}-benzoylamino)-5-piperidin-1-yl-benzoic acid methyl ester (612 mg) produced by the above reaction was dissolved in ethanol (10.0 ml). Hydrazine monohydrate (700 μl) was added to the solution, and the mixture was stirred at room temperature for 15 hr. After the completion of the reaction, water was added thereto at room temperature, and the mixture was subjected to separatory extraction with chloroform. The organic layer was washed with saturated brine, was dried over sodium sulfate, and was then concentrated. The residue was purified by column chromatography eluted with a chloroform-methanol system to give 3-{[(2-diethylamino-ethyl)-methyl-amino]-methyl}-N-(2-hydrazinocarbonyl-4-piperidin-1-yl-phenyl)-benzamide as a hydrazine compound (612 mg, yield 100%).

3-{[(2-Diethylamino-ethyl)-methyl-amino]-methyl}-N-(2-hydrazinocarbonyl-4-piperidin-1-yl-phenyl)-benzamide as a hydrazine compound (70 mg) produced by the above reaction was dissolved in anhydrous toluene (1.0 ml). 3,4-Dimethylbenzaldehyde (compound C) (40 μl) was added to the solution at room temperature, and the mixture was stirred at 70° C. for 15 hr. After the completion of the reaction, the reaction product was purified by column chromatography eluted with a chloroform-methanol system to give the title compound 858 (62 mg, yield 70%).

¹H-NMR (CDCl₃, 400 MHz): δ 1.04 (6H, t, J=7.2 Hz), 1.26 (2H, m), 1.37 (4H, m), 2.26 (9H, m), 2.60 (6H, m), 2.69 (2H, m), 2.84 (4H, m), 3.62 (2H, s), 6.86 (1H, d, J=8.8 Hz), 7.00 (1H, s), 7.15 (1H, d, J=7.6 Hz), 7.44 (1H, dd, J=7.6 Hz, J=7.6 Hz), 7.53 (2H, m), 7.65 (1H, s), 7.89 (1H, d, J=7.6 Hz), 7.98 (1H, s), 8.10 (1H, d, J=8.8 Hz), 8.51 (1H, s), 11.23 (2H, m)

Mass spectrometric value (ESI-MS) 595 (M−1)

Compound 859 3-{[(2-Diethylamino-ethyl)-methyl-amino]-methyl}-N-[2-(4-methyl-benzylidene-hydrazinocarbonyl)-4-piperidin-1-yl-phenyl]-benzamide

The title compound 859 was produced in substantially the same manner as in Example F.

¹H-NMR (CDCl₃, 400 MHz): δ 1.05 (6H, t, J=7.2 Hz), 1.29 (2H, m), 1.40 (4H, m), 2.25 (3H, s), 2.37 (3H, s), 2.62 (6H, m), 2.72 (2H, m), 2.87 (4H, m), 3.62 (2H, s), 6.89 (1H, d, J=8.8 Hz), 7.02 (1H, s), 7.20 (2H, d, J=7.8 Hz), 7.43 (1H, dd, J=7.7 Hz, J=7.7 Hz), 7.53 (1H, d, J=7.3 Hz), 7.72 (2H, d, J=7.6 Hz), 7.88 (1H, d, J=7.6 Hz), 7.97 (1H, s), 8.13 (1H, d, J=9.0 Hz), 8.51 (1H, s), 11.23 (2H, m)

Mass spectrometric value (ESI-MS) 581 (M−1)

Compound 860 3-{[(2-Diethylamino-ethyl)-methyl-amino]-methyl}-N-[2-(4-fluoro-benzylidene-hydrazinocarbonyl)-4-piperidin-1-yl-phenyl]-benzamide

The title compound 860 was produced in substantially the same manner as in Example F.

¹H-NMR (CDCl₃, 400 MHz): δ 1.05 (6H, t, J=7.1 Hz), 1.28 (2H, m), 1.37 (4H, m), 2.25 (3H, s), 2.62 (6H, m), 2.72 (2H, m), 2.84 (4H, m), 3.63 (2H, s), 6.87 (1H, d, J=8.5 Hz), 6.99 (1H, m), 7.09 (2H, dd, J=8.5 Hz, J=8.5 Hz), 7.44 (1H, dd, J=7.6 Hz, J=7.6 Hz), 7.54 (1H, d, J=7.3 Hz), 7.83 (2H, m), 7.88 (1H, d, J=7.4 Hz), 7.98 (1H, s), 8.07 (1H, d, J=9.0 Hz), 8.56 (1H, s), 11.19 (1H, s)

Mass spectrometric value (ESI-MS) 585 (M−1)

Compound 861 3-{[(2-Diethylamino-ethyl)-methyl-amino]-methyl}-N-[2-(3-fluoro-benzylidene-hydrazinocarbonyl)-4-piperidin-1-yl-phenyl]-benzamide

The title compound 861 was produced in substantially the same manner as in Example F.

¹H-NMR (CDCl₃, 400 MHz): δ 1.10 (6H, t, J=7.0 Hz), 1.30 (2H, m), 1.39 (4H, m), 2.25 (3H, s), 2.64-2.90 (12H, m), 3.62 (2H, s), 6.89 (1H, d, J=8.5 Hz), 7.07 (2H, m), 7.27-7.65 (4H, m), 7.68-8.00 (3H, m), 8.11 (1H, d, J=9.0 Hz), 8.53 (1H, s), 11.23 (1H, s)

Mass spectrometric value (ESI-MS) 585 (M−1)

Compound 862 N-[2-(4-Chloro-3-trifluoromethyl-benzylidene-hydrazinocarbonyl)-4-piperidin-1-yl-phenyl]-3-{[(2-diethylamino-ethyl)-methyl-amino]-methyl}-benzamide

The title compound 862 was produced in substantially the same manner as in Example F.

¹H-NMR (CDCl₃, 400 MHz): δ 1.03 (6H, t, J=7.2 Hz), 1.23 (2H, m), 1.32 (4H, m), 2.27 (3H, s), 2.58 (6H, m), 2.67 (2H, m), 2.79 (4H, m), 3.64 (2H, s), 6.81 (1H, d, J=8.5 Hz), 6.92 (1H, s), 7.47 (1H, dd, J=7.7 Hz, J=7.7 Hz), 7.57 (2H, m), 7.88 (1H, d, J=7.8 Hz), 7.95 (1H, d, J=9.0 Hz), 8.01 (1H, s), 8.06 (1H, d, J=8.1 Hz), 8.10 (1H, s), 8.64 (1H, s), 11.08 (1H, s)

Mass spectrometric value (ESI-MS) 669 (M−1)

Compound 863 3-{[(2-Diethylamino-ethyl)-methyl-amino]-methyl}-N-[2-(4-methoxy-benzylidene-hydrazinocarbonyl)-4-piperidin-1-yl-phenyl]-benzamide

The title compound 863 was produced in substantially the same manner as in Example F.

¹H-NMR (CDCl₃, 400 MHz): δ 1.06 (6H, t, J=7.1 Hz), 1.32 (2H, m), 1.43 (4H, m), 2.24 (3H, s), 2.62 (6H, m), 2.72 (2H, m), 2.90 (4H, m), 3.62 (2H, s), 3.82 (3H, s), 6.83-6.95 (3H, m), 7.05 (1H, s), 7.42 (1H, m), 7.52 (1H, m), 7.74 (2H, d, J=8.6 Hz), 7.88 (1H, d, J=7.6 Hz), 7.96 (1H, s), 8.18 (1H, d, J=9.0 Hz), 8.48 (1H, s)

Mass spectrometric value (ESI-MS) 597 (M−1)

Compound 864 N-[2-(3,4-Dimethyl-benzylidene-hydrazinocarbonyl)-4-piperidin-1-yl-phenyl]-3-[4-(2-hydroxy-ethyl)-piperazin-1-ylmethyl]-benzamide

The title compound 864 was produced in substantially the same manner as in Example F.

¹H-NMR (CDCl₃, 400 MHz): δ 1.42 (4H, m), 1.32 (2H, m), 2.28 (3H, s), 2.29 (3H, s), 2.48-2.72 (10H, m), 2.88 (4H, m), 3.61 (4H, m), 6.92 (1H, m), 6.99 (1H, m), 7.16 (1H, d, J=7.8 Hz), 7.44 (1H, dd, J=7.7 Hz, J=7.7 Hz), 7.51 (2H, m), 7.65 (1H, s), 7.90 (1H, d, J=7.8 Hz), 7.99 (1H, s), 8.17 (1H, d, J=9.2 Hz), 8.43 (1H, s), 10.71 (1H, s), 11.21 (1H, s)

Mass spectrometric value (ESI-MS) 595 (M−1)

Compound 865 3-[4-(2-Hydroxy-ethyl)-piperazin-1-ylmethyl]-N-[2-(4-methyl-benzyl idene-hydrazinocarbonyl)-4-piperidin-1-yl-phenyl]-benzamide

The title compound 865 was produced in substantially the same manner as in Example F.

¹H-NMR (CDCl₃, 400 MHz): δ 1.28 (2H, m), 1.39 (4H, m), 2.36 (3H, s), 2.48-2.90 (14H, m), 3.60 (4H, m), 6.88 (1H, d, J=9.0 Hz), 6.99 (1H, s), 7.20 (2H, d, J=8.0 Hz), 7.44 (1H, dd, J=7.6 Hz, J=7.6 Hz), 7.51 (1H, d, J=7.3 Hz), 7.72 (2H, d, J=7.8 Hz), 7.90 (1H, d, J=7.6 Hz), 7.99 (1H, s), 8.13 (1H, d, J=9.0 Hz), 8.49 (1H, s), 10.95 (1H, s), 11.23 (1H, s)

Mass spectrometric value (ESI-MS) 581 (M−1)

Compound 866 N-[2-(4-Fluoro-benzylidene-hydrazinocarbonyl)-4-piperidin-1-yl-phenyl]-3-[4-(2-hydroxy-ethyl)-piperazin-1-ylmethyl]-benzamide

The title compound 866 was produced in substantially the same manner as in Example F.

¹H-NMR (CDCl₃, 400 MHz): δ 1.27 (2H, m), 1.37 (4H, m), 2.55-2.90 (14H, m), 3.62 (2H, s), 3.68 (2H, t, J=5.2 Hz), 6.88 (1H, d, J=8.8 Hz), 7.00-7.16 (2H, m), 7.31-7.60 (4H, m), 7.70-8.03 (3H, m), 8.11 (1H, d, J=9.0 Hz), 8.52 (1H, s), 11.21 (1H, s), 11.35 (1H, s)

Mass spectrometric value (ESI-MS) 585 (M−1)

Compound 867 N-[2-(3-Fluoro-benzylidene-hydrazinocarbonyl)-4-piperidin-1-yl-phenyl]-3-[4-(2-hydroxy-ethyl)-piperazin-1-ylmethyl]-benzamide

The title compound 867 was produced in substantially the same manner as in Example F.

¹H-NMR (CDCl₃, 400 MHz): δ 1.26 (2H, m), 1.36 (4H, m), 2.58 (10H, m), 2.83 (4H, m), 3.62 (4H, m), 6.87 (1H, d, J=8.8 Hz), 6.98 (1H, s), 7.08 (2H, dd, J=8.4 Hz, J=8.4 Hz), 7.44 (1H, dd, J=7.6 Hz, J=7.6 Hz), 7.52 (1H, d, J=7.8 Hz), 7.81 (2H, m), 7.89 (1H, d, J=7.6 Hz), 7.98 (1H, s), 8.09 (1H, d, J=9.0 Hz), 8.53 (1H, s), 11.20 (1H, s)

Mass spectrometric value (ESI-MS) 585 (M−1)

Compound 868 N-[2-(4-Chloro-3-trifluoromethyl-benzylidene-hydrazinocarbonyl)-4-piperidin-1-yl-phenyl]-3-[4-(2-hydroxy-ethyl)-piperazin-1-ylmethyl]-benzamide

The title compound 868 was produced in substantially the same manner as in Example F.

¹H-NMR (CD₃OD, 400 MHz): δ 1.61 (2H, m), 1.72 (4H, m), 2.46-2.65 (10H, m), 3.22 (4H, m), 3.63 (4H, m), 7.20 (1H, dd, J=9.3 Hz, J=2.7 Hz), 7.36 (1H, d, J=2.7 Hz), 7.48 (1H, dd, J=7.7 Hz, J=7.7 Hz), 7.55 (1H, d, J=7.8 Hz), 7.65 (1H, d, J=8.3 Hz), 7.86 (1H, m), 7.93 (1H, m), 8.00 (1H, d, J=8.3 Hz), 8.26 (1H, s), 8.32 (1H, d, J=9.3 Hz), 8.36 (1H, s)

Mass spectrometric value (ESI-MS) 669 (M−1)

Compound 869 3-[4-(2-Hydroxy-ethyl)-piperazin-1-ylmethyl]-N-[2-(4-methoxy-benzylidene-hydrazinocarbonyl)-4-piperidin-1-yl-phenyl]-benzamide

The title compound 869 was produced in substantially the same manner as in Example F.

¹H-NMR (CDCl₃, 400 MHz): δ 1.37 (2H, m), 1.48 (4H, m), 2.56 (10H, m), 2.93 (4H, m), 3.61 (4H, m), 3.84 (3H, s), 6.90-7.04 (4H, m), 7.44 (1H, dd, J=7.4 Hz, J=7.4 Hz), 7.51 (1H, d, J=7.4 Hz), 7.76 (2H, d, J=8.3 Hz), 7.89 (1H, d, J=7.6 Hz), 7.98 (1H, s), 8.23 (1H, m), 8.38 (1H, m), 11.21 (1H, s)

Mass spectrometric value (ESI-MS) 597 (M−1)

Compound 870 N-[2-(3,4-Dimethyl-benzylidene-hydrazinocarbonyl)-4-piperidin-1-yl-phenyl]-3-(4-hydroxy-piperidin-1-ylmethyl)-benzamide

The title compound 870 was produced in substantially the same manner as in Example F.

¹H-NMR (CDCl₃, 400 MHz): δ 1.32 (2H, m), 1.43 (4H, m), 1.63 (2H, m), 1.90 (2H, m), 2.29 (8H, m), 2.80 (2H, m), 2.88 (4H, m), 3.63 (2H, s), 3.72 (1H, m), 6.91 (1H, d, J=8.8 Hz), 7.02 (1H, s), 7.15 (1H, d, J=7.8 Hz), 7.35-7.55 (3H, m), 7.65 (1H, m), 7.90 (1H, d, J=7.3 Hz), 7.97 (1H, s), 8.18 (1H, d, J=9.3 Hz), 8.44 (1H, s), 10.79 (1H, s), 11.24 (1H, s)

Mass spectrometric value (ESI-MS) 566 (M−1)

Compound 871 3-(4-Hydroxy-piperidin-1-ylmethyl)-N-[2-(4-methyl-benzylidene-hydrazinocarbonyl)-4-piperidin-1-yl-phenyl]-benzamide

The title compound 871 was produced in substantially the same manner as in Example F.

¹H-NMR (CDCl₃, 400 MHz): δ 1.26 (2H, m), 1.40 (4H, m), 1.64 (2H, m), 1.89 (2H, m), 2.26 (2H, m), 2.35 (3H, s), 2.82 (6H, m), 3.63 (2H, s), 3.71 (1H, m), 6.89 (1H, d, J=8.6 Hz), 7.04 (1H, s), 7.18 (2H, d, J=7.8 Hz), 7.43 (1H, m), 7.53 (1H, m), 7.69 (2H, d, J=7.6 Hz), 7.90 (1H, d, J=7.3 Hz), 7.97 (1H, s), 8.17 (1H, d, J=8.6 Hz), 8.47 (1H, s), 10.98 (1H, s), 11.26 (1H, s)

Mass spectrometric value (ESI-MS) 552 (M−1)

Compound 872 N-[2-(4-Fluoro-benzylidene-hydrazinocarbonyl)-4-piperidin-1-yl-phenyl]-3-(4-hydroxy-piperidin-1-ylmethyl)-benzamide

The title compound 872 was produced in substantially the same manner as in Example F.

¹H-NMR (CDCl₃, 400 MHz): δ 1.32 (2H, m), 1.42 (4H, m), 1.66 (2H, m), 1.92 (2H, m), 2.40 (2H, m), 2.88 (6H, m), 3.71 (2H, s), 3.76 (1H, m), 6.90 (1H, d, J=8.8 Hz), 6.98-7.11 (2H, m), 7.43 (1H, m), 7.54 (1H, m), 7.77 (2H, m), 7.89 (1H, d, J=7.6 Hz), 7.96 (1H, s), 8.05 (1H, m), 8.15 (1H, d, J=9.0 Hz), 8.47 (1H, s), 11.10-11.30 (2H, m)

Mass spectrometric value (ESI-MS) 556 (M−1)

Compound 873 N-[2-(3-Fluoro-benzylidene-hydrazinocarbonyl)-4-piperidin-1-yl-phenyl]-3-(4-hydroxy-piperidin-1-ylmethyl)-benzamide

The title compound 873 was produced in substantially the same manner as in Example F.

¹H-NMR (CDCl₃, 400 MHz): δ 1.34 (2H, m), 1.44 (4H, m), 1.67 (2H, m), 1.94 (2H, m), 2.34 (2H, m), 2.88 (6H, m), 3.70 (2H, s), 3.77 (1H, m), 6.92 (1H, d, J=8.3 Hz), 7.09 (3H, m), 7.29-7.67 (4H, m), 7.90 (1H, d, J=7.8 Hz), 7.97 (1H, s), 8.14 (1H, d, J=9.0 Hz), 8.49 (1H, s), 11.02 (1H, s), 11.17 (1H, s)

Mass spectrometric value (ESI-MS) 556 (M−1)

Compound 874 N-[2-(4-Chloro-3-trifluoromethyl-benzylidene-hydrazinocarbonyl)-4-piperidin-1-yl-phenyl]-3-(4-hydroxy-piperidin-1-ylmethyl)-benzamide

The title compound 874 was produced in substantially the same manner as in Example F.

¹H-NMR (CD₃OD, 400 MHz): δ 1.50-1.68 (4H, m), 1.75 (4H, m), 1.84 (2H, m), 2.22 (2H, m), 2.81 (2H, m), 3.24 (4H, t, J=5.2 Hz), 3.61 (3H, m), 7.22 (1H, dd, J=9.0 Hz, J=2.7 Hz), 7.37 (1H, d, J=2.7 Hz), 7.50 (1H, m), 7.57 (1H, m), 7.67 (1H, d, J=8.3 Hz), 7.87 (1H, d, J=7.8 Hz), 7.92 (1H, s), 8.03 (1H, d, J=8.3 Hz), 8.29 (1H, s), 8.33 (1H, d, J=9.0 Hz), 8.37 (1H, s)

Mass spectrometric value (ESI-MS) 640 (M−1)

Compound 875 3-(4-Hydroxy-piperidin-1-ylmethyl)-N-[2-(4-methoxy-benzylidene-hydrazinocarbonyl)-4-piperidin-1-yl-phenyl]-benzamide

The title compound 875 was produced in substantially the same manner as in Example F.

¹H-NMR (CDCl₃, 400 MHz): δ 1.34 (2H, m), 1.45 (4H, m), 1.64 (2H, m), 1.90 (2H, m), 2.25 (2H, m), 2.79 (2H, m), 2.91 (4H, m), 3.63 (2H, s), 3.72 (1H, m), 3.83 (3H, m), 6.92 (3H, m), 7.64 (1H, s), 7.33-7.50 (1H, m), 7.53 (1H, d, J=7.6 Hz), 7.75 (2H, d, J=8.3 Hz), 7.89 (1H, d, J=7.6 Hz), 7.96 (1H, s), 8.22 (1H, d, J=8.8 Hz), 8.42 (1H, s), 10.68 (1H, bs), 11.25 (1H, s)

Mass spectrometric value (ESI-MS) 568 (M−1)

Compound 876 3-(2-Diethylamino-ethylsulfanylmethyl)-N-[2-(3,4-dimethyl-benzylidene-hydrazinocarbonyl)-4-piperidin-1-yl-phenyl]-benzamide

The title compound 876 was produced in substantially the same manner as in Example F.

¹H-NMR (CDCl₃, 400 MHz): δ 1.03 (6H, t, J=7.1 Hz), 1.33 (2H, m), 1.44 (4H, m), 2.29 (6H, m), 2.59 (6H, m), 2.71 (2H, m), 2.90 (4H, m), 3.84 (2H, s), 6.92 (1H, d, J=8.8 Hz), 7.10 (1H, s), 7.16 (1H, d, J=7.6 Hz), 7.44 (1H, dd, J=7.6 Hz, J=7.6 Hz), 7.53 (2H, m), 7.66 (1H, m), 7.89 (1H, d, J=7.6 Hz), 8.00 (1H, s), 8.18 (1H, d, J=8.8 Hz), 8.44 (1H, s), 10.73 (1H, bs), 11.26 (1H, s)

Mass spectrometric value (ESI-MS) 598 (M−1)

Compound 877 3-(2-Diethylamino-ethylsulfanylmethyl)-N-[2-(4-fluoro-benzylidene-hydrazinocarbonyl)-4-piperidin-1-yl-phenyl]-benzamide

The title compound 877 was produced in substantially the same manner as in Example F.

¹H-NMR (CDCl₃, 400 MHz): δ 1.08 (6H, t, J=7.0 Hz), 1.36 (2H, m), 1.46 (4H, m), 2.74 (6H, m), 2.84 (2H, m), 2.92 (4H, m), 3.83 (2H, s), 6.94 (1H, d, J=8.3 Hz), 7.05 (2H, m), 7.42 (1H, d, J=7.7 Hz, J=7.7 Hz), 7.52 (1H, m), 7.79 (2H, m), 7.88 (1H, d, J=7.6 Hz), 7.98 (1H, s), 8.03 (1H, m), 8.17 (1H, d, J=8.8 Hz), 8.47 (1H, s), 11.02 (1H, bs), 11.27 (1H, s)

Mass spectrometric value (ESI-MS) 588 (M−1)

Compound 878 N-[2-(4-Chloro-3-trifluoromethyl-benzylidene-hydrazinocarbonyl)-4-piperidin-1-yl-phenyl]-3-(2-diethylamino-ethylsulfanylmethyl)-benzamide

The title compound 878 was produced in substantially the same manner as in Example F.

¹H-NMR (CDCl₃, 400 MHz): δ 1.03 (6H, m), 1.29 (2H, m), 1.38 (4H, m), 2.48-2.75 (8H, m), 2.84 (4H, m), 3.85 (2H, s), 6.90 (2H, m), 7.47 (1H, dd, J=7.6 Hz, J=7.6 Hz), 7.56 (2H, m), 7.88 (1H, d, J=7.8 Hz), 8.00-8.12 (4H, m), 8.60 (1H, s), 11.07 (2H, m)

Mass spectrometric value (ESI-MS) 672 (M−1)

Compound 879 3-(2-Diethylamino-ethylsulfanylmethyl)-N-[2-(4-methoxy-benzylidene-hydrazinocarbonyl)-4-piperidin-1-yl-phenyl]-benzamide

The title compound 879 was produced in substantially the same manner as in Example F.

¹H-NMR (CDCl₃, 400 MHz): δ 1.02 (6H, t, J=7.1 Hz), 1.26 (2H, m), 1.67 (4H, m), 2.59 (6H, m), 2.70 (2H, m), 2.92 (4H, m), 3.83 (5H, m), 6.92 (3H, m), 7.02 (1H, s), 7.44 (1H, dd, J=7.6 Hz, J=7.6 Hz), 7.53 (1H, d, J=7.6 Hz), 7.77 (2H, d, J=8.3 Hz), 7.88 (1H, d, J=7.6 Hz), 7.99 (1H, m), 8.22 (1H, d, J=8.8 Hz), 8.42 (1H, s), 10.59 (1H, bs), 11.27 (1H, s)

Mass spectrometric value (ESI-MS) 600 (M−1)

Compound 880 N-[2-(3,4-Dimethyl-benzylidene-hydrazinocarbonyl)-4-piperidin-1-yl-phenyl]-3-(2-hydroxy-ethylsulfanylmethyl)-benzamide

The title compound 880 was produced in substantially the same manner as in Example F.

¹H-NMR (CDCl₃, 400 MHz): δ 1.41 (2H, m), 1.51 (4H, m), 2.24 (3H, s), 2.67 (3H, s), 2.65 (2H, t, J=6.9 Hz), 2.94 (4H, m), 3.82 (2H, s), 3.93 (1H, t, J=6.8 Hz), 6.93 (1H, d, J=9.0 Hz), 7.04 (1H, s), 7.14 (1H, d, J=7.8 Hz), 7.52 (3H, m), 7.63 (1H, s), 7.80 (1H, s), 8.01 (1H, d, J=6.8 Hz), 8.25 (1H, s), 8.28 (2H, d, J=9.0 Hz), 10.56 (1H, s), 11.50 (1H, s)

Mass spectrometric value (ESI-MS) 543 (M−1)

Compound 881 3-(2-Hydroxy-ethylsulfanylmethyl)-N-[2-(4-methyl-benzylidene-hydrazinocarbonyl)-4-piperidin-1-yl-phenyl]-benzamide

The title compound 881 was produced in substantially the same manner as in Example F.

¹H-NMR (CDCl₃, 400 MHz): δ 1.43 (2H, m), 1.54 (4H, m), 2.33 (3H, s), 2.64 (2H, t, J=7.1 Hz), 2.97 (4H, m), 3.82 (2H, s), 3.92 (2H, m), 6.95 (1H, m), 7.08 (1H, s), 7.19 (2H, d, J=7.8 Hz), 7.54 (2H, m), 7.69 (2H, d, J=7.8 Hz), 7.79 (1H, s), 8.00 (1H, d, J=7.1 Hz), 8.26 (1H, s), 8.30 (1H, d, J=9.3 Hz), 10.52 (1H, s), 11.49 (1H, s)

Mass spectrometric value (ESI-MS) 529 (M−1)

Compound 882 N-[2-(4-Fluoro-benzylidene-hydrazinocarbonyl)-4-piperidin-1-yl-phenyl]-3-(2-hydroxy-ethylsulfanylmethyl)-benzamide

The title compound 882 was produced in substantially the same manner as in Example F.

¹H-NMR (CDCl₃, 400 MHz): δ 1.44 (2H, m), 1.57 (4H, m), 2.64 (2H, t, J=7.0 Hz), 2.99 (4H, m), 3.81 (2H, s), 3.91 (2H, m), 7.00 (1H, d, J=8.8 Hz), 7.10 (2H, dd, J=8.7 Hz, J=8.7 Hz), 7.15 (1H, s), 7.54 (2H, m), 7.78 (1H, s), 7.86 (2H, m), 8.06 (1H, d, J=7.1 Hz), 8.33 (2H, m), 10.59 (1H, s), 11.48 (1H, s)

Mass spectrometric value (ESI-MS) 533 (M−1)

Compound 883 N-[2-(3-Fluoro-benzylidene-hydrazinocarbonyl)-4-piperidin-1-yl-phenyl]-3-(2-hydroxy-ethylsulfanylmethyl)-benzamide

The title compound 883 was produced in substantially the same manner as in Example F.

¹H-NMR (CDCl₃, 400 MHz): δ 1.44 (2H, m), 1.57 (4H, m), 2.65 (2H, t, J=6.9 Hz), 2.99 (4H, m), 3.82 (2H, s), 3.92 (2H, m), 6.80-7.22 (3H, m), 7.36 (1H, m), 7.53 (3H, m), 7.66 (1H, m), 7.80 (1H, s), 8.00 (1H, d, J=6.6 Hz), 8.30 (2H, m), 10.65 (1H, s), 11.46 (1H, s)

Mass spectrometric value (ESI-MS) 533 (M−1)

Compound 884 N-[2-(4-Chloro-3-trifluoromethyl-benzylidene-hydrazinocarbonyl)-4-piperidin-1-yl-phenyl]-3-(2-hydroxy-ethylsulfanylmethyl)-benzamide

The title compound 884 was produced in substantially the same manner as in Example F.

¹H-NMR (CDCl₃, 400 MHz): δ 1.36 (2H, m), 1.44 (4H, m), 2.65 (2H, t, J=7.2 Hz), 2.86 (4H, m), 3.82 (2H, s), 3.92 (2H, t, J=7.1 Hz), 6.90 (1H, d, J=8.0 Hz), 6.97 (1H, s), 7.57 (3H, m), 7.76 (1H, s), 8.04 (2H, d, J=6.8 Hz), 8.14 (1H, d, J=9.8 Hz), 8.23 (1H, s), 8.43 (1H, s), 11.09 (1H, s), 11.38 (1H, s)

Mass spectrometric value (ESI-MS) 617 (M−1)

Compound 885 3-(2-Hydroxy-ethylsulfanylmethyl)-N-[2-(4-methoxy-benzylidene-hydrazinocarbonyl)-4-piperidin-1-yl-phenyl]-benzamide

The title compound 885 was produced in substantially the same manner as in Example F.

¹H-NMR (CDCl₃, 400 MHz): δ 1.47 (2H, m), 1.62 (4H, m), 2.64 (2H, t, J=7.1 Hz), 3.04 (4H, m), 3.80 (3H, s), 3.81 (2H, s), 3.92 (2H, m), 6.89 (2H, d, J=8.8 Hz), 7.02 (1H, m), 7.24 (1H, m), 7.52 (2H, m), 7.76 (3H, m), 7.99 (1H, d, J=7.3 Hz), 8.25 (1H, s), 8.40 (1H, d, J=9.0 Hz), 10.50 (1H, s), 11.59 (1H, s)

Mass spectrometric value (ESI-MS) 545 (M−1)

Compound 886 3-{3-[2-(3,4-Dimethyl-benzylidene-hydrazinocarbonyl)-4-piperidin-1-yl-phenylcarbamoyl]-benzylsulfanyl}-propionic acid

The title compound 886 was produced in substantially the same manner as in Example F.

¹H-NMR (CDCl₃, 400 MHz): δ 1.37 (2H, m), 1.52 (4H, m), 2.20 (6H, s), 2.75 (2H, m), 2.84 (2H, m), 2.94 (4H, m), 3.94 (2H, s), 6.93 (1H, d, J=7.8 Hz), 7.06 (1H, d, J=7.6 Hz), 7.11 (1H, s), 7.38-7.52 (3H, m), 7.55 (1H, s), 7.94 (1H, s), 8.02 (1H, d, J=6.8 Hz), 8.25 (1H, d, J=9.0 Hz), 8.28 (1H, s), 10.85 (1H, s), 11.36 (1H, s)

Mass spectrometric value (ESI-MS) 571 (M−1)

Compound 887 3-{3-[2-(4-Methyl-benzylidene-hydrazinocarbonyl)-4-piperidin-1-yl-phenylcarbamoyl]-benzylsulfanyl}-propionic acid

The title compound 887 was produced in substantially the same manner as in Example F.

¹H-NMR (CDCl₃, 400 MHz): δ 1.33 (2H, m), 1.47 (4H, m), 2.29 (3H, s), 2.70 (2H, t, J=6.4 Hz), 2.80 (2H, t, J=6.3 Hz), 2.90 (4H, m), 3.89 (2H, s), 6.91 (1H, d, J=8.8 Hz), 7.12 (3H, m), 7.40-7.50 (2H, m), 7.61 (2H, d, J=7.8 Hz), 7.93 (1H, s), 7.97 (1H, d, J=7.3 Hz), 8.20 (1H, d, J=9.0 Hz), 8.35 (1H, s), 11.03 (1H, s), 11.32 (1H, s)

Mass spectrometric value (ESI-MS) 557 (M−1)

Compound 888 3-{3-[2-(4-Fluoro-benzylidene-hydrazinocarbonyl)-4-piperidin-1-yl-phenylcarbamoyl]-benzylsulfanyl}-propionic acid

The title compound 888 was produced in substantially the same manner as in Example F.

¹H-NMR (CD₃OD, 400 MHz): δ 1.62 (2H, m), 1.74 (4H, m), 2.55 (2H, t, J=6.8 Hz), 2.68 (2H, t, J=7.0 Hz), 3.23 (4H, m), 3.86 (2H, s), 7.10-7.25 (3H, m), 7.36 (1H, d, J=2.9 Hz), 7.47 (1H, dd, J=7.1 Hz, J=7.1 Hz), 7.57 (1H, d, J=7.3 Hz), 7.85 (3H, m), 7.93 (1H, m), 8.32 (2H, m)

Mass spectrometric value (ESI-MS) 561 (M−1)

Compound 889 3-{3-[2-(4-Chloro-3-trifluoromethyl-benzylidene-hydrazinocarbonyl)-4-piperidin-1-yl-phenylcarbamoyl]-benzylsulfanyl}-propionic acid

The title compound 889 was produced in substantially the same manner as in Example F.

¹H-NMR (CD₃OD, 400 MHz): δ 1.62 (2H, m), 1.74 (4H, m), 2.54 (2H, t, J=7.0 Hz), 2.68 (2H, t, J=7.0 Hz), 3.22 (4H, m), 3.86 (2H, s), 7.22 (1H, m), 7.36 (1H, m), 7.48 (1H, dd, J=7.6 Hz, J=7.6 Hz), 7.57 (1H, m), 7.67 (1H, m), 7.83 (1H, d, J=7.3 Hz), 7.93 (1H, s), 8.03 (1H, d, J=9.0 Hz), 8.29 (2H, m), 8.36 (1H, m)

Mass spectrometric value (ESI-MS) 646 (M−1)

Compound 890 3-{3-[2-(4-Methoxy-benzylidene-hydrazinocarbonyl)-4-piperidin-1-yl-phenylcarbamoyl]-benzylsulfanyl}-propionic acid

The title compound 890 was produced in substantially the same manner as in Example F.

¹H-NMR (CDCl₃, 400 MHz): δ 1.35 (2H, m), 1.49 (4H, m), 2.71 (2H, m), 2.80 (2H, m), 2.92 (4H, m), 3.76 (3H, s), 3.89 (2H, s), 6.80 (2H, d, J=8.8 Hz), 6.92 (1H, d, J=7.3 Hz), 7.15 (1H, s), 7.45 (2H, m), 7.64 (2H, d, J=8.6 Hz), 7.95 (2H, m), 8.24 (1H, d, J=9.0 Hz), 8.31 (1H, s), 10.97 (1H, bs), 11.37 (1H, s)

Mass spectrometric value (ESI-MS) 573 (M−1)

Compound 891 {3-[2-(4-Chloro-3-trifluoromethyl-benzylidene-hydrazinocarbonyl)-4-piperidin-1-yl-phenylcarbamoyl]-benzylsulfanyl}-acetic acid

The title compound 891 was produced in substantially the same manner as in Example F.

¹H-NMR (CD₃OD, 400 MHz): δ 1.63 (2H, m), 1.75 (4H, m), 3.11 (2H, s), 3.24 (4H, m), 3.94 (2H, s), 7.22 (1H, dd, J=9.2 Hz, J=2.8 Hz), 7.37 (1H, d, J=2.7 Hz), 7.48 (1H, dd, J=7.7 Hz, J=7.7 Hz), 7.58 (1H, d, J=8.0 Hz), 7.67 (1H, d, J=8.3 Hz), 7.84 (1H, d, J=8.0 Hz), 7.95 (1H, s), 8.03 (1H, d, J=8.6 Hz), 8.28 (2H, m), 8.37 (1H, s)

Mass spectrometric value (ESI-MS) 631 (M−1)

Compound 892 {3-[2-(4-Methoxy-benzylidene-hydrazinocarbonyl)-4-piperidin-1-yl-phenylcarbamoyl]-benzylsulfanyl}-acetic acid

The title compound 892 was produced in substantially the same manner as in Example F.

¹H-NMR (CDCl₃, 400 MHz): δ 1.39 (2H, m), 1.53 (4H, m), 2.93 (4H, m), 3.21 (2H, s), 3.77 (3H, s), 3.98 (2H, s), 6.82 (2H, d, J=8.6 Hz), 6.93 (1H, d, J=9.3 Hz), 7.22 (1H, s), 7.48 (2H, m), 7.63 (2H, d, J=8.3 Hz), 7.82 (1H, s), 7.98 (1H, d, J=7.1 Hz), 8.25 (1H, d, J=8.8 Hz), 8.32 (1H, s), 10.93 (1H, s), 11.43 (1H, s)

Mass spectrometric value (ESI-MS) 559 (M−1)

Compound 893 3-(7,8-Dihydro-5H-1,6,9-triaza-anthracen-6-ylmethyl)-N-[2-(3,4-dimethyl-benzylidene-hydrazinocarbonyl)-4-piperidin-1-yl-phenyl]-benzamide

The title compound 893 was produced in substantially the same manner as in Example F.

¹H-NMR (CDCl₃, 400 MHz): δ 1.32 (2H, m), 1.40 (4H, m), 2.22 (6H, s), 2.83 (4H, m), 2.97 (2H, t, J=5.7 Hz), 3.31 (2H, t, J=6.0 Hz), 3.84 (4H, s), 6.92 (1H, d, J=9.0 Hz), 7.09 (2H, m), 7.35 (1H, m), 7.45 (2H, m), 7.61 (2H, m), 7.77 (1H, s), 7.95 (1H, d, J=7.3 Hz), 8.02 (2H, m), 8.26 (1H, d, J=9.0 Hz), 8.49 (1H, s), 8.97 (1H, dd, J=4.3 Hz, J=1.8 Hz), 11.05 (1H, s), 11.41 (1H, s)

Mass spectrometric value (ESI-MS) 650 (M−1)

Compound 894 3-(7,8-Dihydro-5H-1,6,9-triaza-anthracen-6-ylmethyl)-N-[2-(4-methyl-benzylidene-hydrazinocarbonyl)-4-piperidin-1-yl-phenyl]-benzamide

The title compound 894 was produced in substantially the same manner as in Example F.

¹H-NMR (CDCl₃, 400 MHz): δ 1.31 (2H, m), 1.39 (4H, m), 2.33 (3H, s), 2.82 (4H, m), 2.97 (2H, m), 3.31 (2H, t, J=6.0 Hz), 3.84 (4H, m), 6.92 (1H, d, J=8.1 Hz), 7.07 (1H, s), 7.15 (2H, d, J=8.1 Hz), 7.35 (1H, m), 7.47 (1H, dd, J=7.6 Hz, J=7.6 Hz), 7.60 (1H, d, J=7.3 Hz), 7.65 (2H, d, J=7.1 Hz), 7.77 (1H, s), 7.94 (1H, d, J=7.3 Hz), 8.02 (2H, m), 8.26 (1H, d, J=9.0 Hz), 8.52 (1H, s), 8.97 (1H, dd, J=4.3 Hz, J=1.8 Hz), 11.08 (1H, s), 11.39 (1H, s)

Mass spectrometric value (ESI-MS) 636 (M−1)

Compound 895 3-(7,8-Dihydro-5H-1,6,9-triaza-anthracen-6-ylmethyl)-N-[2-(4-fluoro-benzylidene-hydrazinocarbonyl)-4-piperidin-1-yl-phenyl]-benzamide

The title compound 895 was produced in substantially the same manner as in Example F.

¹H-NMR (CDCl₃, 400 MHz): δ 1.20-1.40 (6H, m), 2.75 (4H, m), 2.94 (2H, m), 3.25 (2H, m), 3.82 (2H, s), 3.83 (2H, s), 6.89 (1H, d, J=8.8 Hz), 7.00 (2H, m), 7.10 (1H, s), 7.37 (1H, m), 7.46 (1H, dd, J=7.7 Hz, J=7.7 Hz), 7.59 (1H, d, J=7.3 Hz), 7.70 (2H, m), 7.77 (1H, s), 7.94 (1H, d, J=7.8 Hz), 8.04 (2H, m), 8.26 (1H, d, J=9.0 Hz), 8.61 (1H, s), 8.94 (1H, m), 11.45-11.75 (2H, m)

Mass spectrometric value (ESI-MS) 640 (M−1)

Compound 896 3-(7,8-Dihydro-5H-1,6,9-triaza-anthracen-6-ylmethyl)-N-[2-(3-fluoro-benzylidene-hydrazinocarbonyl)-4-piperidin-1-yl-phenyl]-benzamide

The title compound 896 was produced in substantially the same manner as in Example F.

¹H-NMR (CDCl₃, 400 MHz): δ 1.29 (2H, m), 1.36 (4H, m), 2.79 (4H, m), 2.97 (2H, m), 3.28 (2H, t, J=6.0 Hz), 3.84 (2H, s), 3.85 (2H, s), 6.90 (1H, d, J=8.3 Hz), 7.03 (1H, m), 7.09 (1H, s), 7.28-8.00 (5H, m), 7.61 (1H, d, J=7.3 Hz), 7.77 (1H, s), 7.94 (1H, d, J=7.6 Hz), 8.05 (2H, m), 8.22 (1H, d, J=9.0 Hz), 8.60 (1H, s), 8.97 (1H, dd, J=4.1 Hz, J=2.0 Hz), 11.38 (1H, s), 11.55 (1H, s)

Mass spectrometric value (ESI-MS) 640 (M−1)

Compound 897 N-[2-(4-Chloro-3-trifluoromethyl-benzylidene-hydrazinocarbonyl)-4-piperidin-1-yl-phenyl]-3-(7,8-dihydro-5H-1,6,9-triaza-anthracen-6-ylmethyl)-benzamide

The title compound 897 was produced in substantially the same manner as in Example F.

¹H-NMR (CDCl₃, 400 MHz): δ 1.30 (2H, m), 1.37 (4H, m), 2.80 (4H, m), 2.97 (2H, t, J=5.9 Hz), 3.30 (2H, t, J=5.9 Hz), 3.86 (4H, m), 6.90 (1H, d, J=8.3 Hz), 7.02 (1H, s), 7.38 (1H, m), 7.51 (2H, d, J=8.3 Hz), 7.62 (1H, d, J=8.3 Hz), 7.78 (1H, s), 7.94 (2H, d, J=7.3 Hz), 8.00 (1H, s), 8.06 (2H, m), 8.17 (1H, d, J=8.3 Hz), 8.61 (1H, s), 8.98 (1H, m), 11.25 (1H, s), 11.46 (1H, s)

Mass spectrometric value (ESI-MS) 724 (M−1)

Compound 898 3-(7,8-Dihydro-5H-1,6,9-triaza-anthracen-6-ylmethyl)-N-[2-(4-methoxy-benzylidene-hydrazinocarbonyl)-4-piperidin-1-yl-phenyl]-benzamide

The title compound 898 was produced in substantially the same manner as in Example F.

¹H-NMR (CDCl₃, 400 MHz): δ 1.31 (2H, m), 1.39 (4H, m), 2.83 (4H, m), 2.97 (2H, m), 3.30 (2H, t, J=5.6 Hz), 3.78 (5H, m), 3.83 (2H, s), 6.85 (2H, d, J=8.0 Hz), 6.92 (1H, d, J=7.1 Hz), 7.09 (1H, s), 7.35 (1H, m), 7.46 (1H, t, J=7.7 Hz), 7.59 (1H, d, J=7.6 Hz), 7.67 (2H, d, J=7.8 Hz), 7.76 (1H, s), 7.94 (1H, d, J=7.6 Hz), 8.02 (2H, m), 8.28 (1H, d, J=9.0 Hz), 8.49 (1H, s), 8.96 (1H, m), 11.08 (1H, bs), 11.44 (1H, s)

Mass spectrometric value (ESI-MS) 652 (M−1)

Compound 899 3-(2,3-Dihydroxy-propylsulfanylmethyl)-N-[2-(3,4-dimethyl-benzylidene-hydrazinocarbonyl)-4-piperidin-1-yl-phenyl]-benzamide

The title compound 899 was produced in substantially the same manner as in Example F.

¹H-NMR (CD₃OD, 400 MHz): δ 1.62 (2H, m), 1.75 (4H, m), 2.29 (3H, s), 2.31 (3H, s), 2.50 (1H, m), 2.63 (1H, m), 3.23 (4H, m), 3.56 (2H, m), 3.74 (1H, m), 3.88 (2H, s), 7.21 (2H, m), 7.37 (1H, d, J=2.9 Hz), 7.48 (1H, dd, J=7.7 Hz, J=7.7 Hz), 7.53 (1H, d, J=7.8 Hz), 7.59 (1H, d, J=7.6 Hz), 7.65 (1H, s), 7.85 (1H, m), 7.93 (1H, m), 8.29 (1H, s), 8.37 (1H, d, J=9.2 Hz)

Mass spectrometric value (ESI-MS) 573 (M−1)

Compound 900 3-(2,3-Dihydroxy-propylsulfanylmethyl)-N-[2-(4-methyl-benzylidene-hydrazinocarbonyl)-4-piperidin-1-yl-phenyl]benzamide

The title compound 900 was produced in substantially the same manner as in Example F.

¹H-NMR (DMSO-d₆, 400 MHz): δ 1.57 (2H, m), 1.67 (4H, m), 2.35 (3H, s), 2.40 (1H, m), 2.58 (1H, m), 3.15-3.36 (6H, m), 3.60 (1H, m), 3.86 (2H, s), 4.55 (1H, m), 4.81 (1H, m), 7.19 (1H, m), 7.28 (2H, d, J=8.1 Hz), 7.32 (1H, d, J=2.4 Hz), 7.53 (2H, m), 7.65 (2H, d, J=8.1 Hz), 7.77 (1H, m), 7.87 (1H, s), 8.29 (1H, d, J=8.3 Hz), 8.41 (1H, s), 11.42 (1H, bs), 11.95 (1H, bs)

Mass spectrometric value (ESI-MS) 559 (M−1)

Compound 901 3-(2,3-Dihydroxy-propylsulfanylmethyl)-N-[2-(4-fluoro-benzylidene-hydrazinocarbonyl)-4-piperidin-1-yl-phenyl]-benzamide

The title compound 901 was produced in substantially the same manner as in Example F.

¹H-NMR (CD₃OD, 400 MHz): δ 1.62 (2H, m), 1.74 (4H, m), 2.50 (1H, m), 2.62 (1H, m), 3.23 (4H, m), 3.55 (2H, m), 3.75 (1H, m), 3.88 (2H, s), 7.17 (2H, dd, J=8.7 Hz, J=8.7 Hz), 7.22 (1H, dd, J=9.0 Hz, J=2.7 Hz), 7.37 (1H, d, J=2.7 Hz), 7.48 (1H, dd, J=7.5 Hz, J=7.5 Hz), 7.58 (1H, d, J=7.6 Hz), 7.80-7.95 (4H, m), 8.34 (1H, s), 8.37 (1H, d, J=9.3 Hz)

Mass spectrometric value (ESI-MS) 563 (M−1)

Compound 902 3-(2,3-Dihydroxy-propylsulfanylmethyl)-N-[2-(3-fluoro-benzylidene-hydrazinocarbonyl)-4-piperidin-1-yl-phenyl]-benzamide

The title compound 902 was produced in substantially the same manner as in Example F.

¹H-NMR (DMSO-d₆, 400 MHz): δ 1.57 (2H, m), 1.67 (4H, m), 2.04 (1H, m), 2.58 (1H, m), 3.19-3.40 (6H, m), 3.60 (1H, m), 3.86 (2H, s), 4.54 (1H, t, J=5.7 Hz), 4.80 (1H, d, J=3.5 Hz), 7.20 (1H, m), 7.29 (2H, m), 7.44-7.64 (5H, m), 7.76 (1H, d, J=7.6 Hz), 7.87 (1H, s), 8.25 (1H, d, J=9.0 Hz), 8.44 (1H, s), 11.30 (1H, s), 12.10 (1H, s)

Mass spectrometric value (ESI-MS) 563 (M−1)

Compound 903 N-[2-(4-Chloro-3-trifluoromethyl-benzylidene-hydrazinocarbonyl)-4-piperidin-1-yl-phenyl]-3-(2,3-dihydroxy-propyl-sulfanylmethyl)-benzamide

The title compound 903 was produced in substantially the same manner as in Example F.

¹H-NMR (CD₃OD, 400 MHz): δ 1.63 (2H, m), 1.75 (4H, m), 2.50 (1H, m), 2.62 (1H, m), 3.24 (4H, m), 3.54 (2H, m), 3.74 (1H, m), 3.88 (2H, s), 7.23 (1H, dd, J=9.1 Hz, J=2.8 Hz), 7.38 (1H, d, J=2.7 Hz), 7.48 (1H, dd, J=7.7 Hz, J=7.7 Hz), 7.58 (1H, d, J=7.8 Hz), 7.68 (1H, d, J=8.3 Hz), 7.84 (1H, d, J=7.8 Hz), 7.93 (1H, s), 8.06 (1H, d, J=8.3 Hz), 8.29 (1H, s), 8.34 (1H, d, J=9.0 Hz), 8.37 (1H, s)

Mass spectrometric value (ESI-MS) 647 (M−1)

Compound 904 3-(2,3-Dihydroxy-propylsulfanylmethyl)-N-[2-(4-methoxy-benzylidene-hydrazinocarbonyl)-4-piperidin-1-yl-phenyl]-benzamide

The title compound 904 was produced in substantially the same manner as in Example F.

¹H-NMR (DMSO-d₆, 400 MHz): δ 1.57 (2H, m), 1.68 (4H, m), 2.40 (1H, m), 2.58 (1H, m), 3.15-3.40 (6H, m), 3.61 (1H, m), 3.82 (3H, s), 3.86 (2H, s), 7.02 (2H, d, J=8.8 Hz), 7.21 (1H, m), 7.33 (1H, m), 7.53 (2H, m), 7.70 (2H, d, J=8.8 Hz), 7.77 (1H, d, J=7.6 Hz), 7.87 (1H, s), 8.31 (1H, d, J=9.0 Hz), 8.39 (1H, s), 11.44 (1H, s), 11.87 (1H, s)

Mass spectrometric value (ESI-MS) 575 (M−1)

Compound 905 3-{[Bis-(2-diethylamino-ethyl)-amino]-methyl}-N-[2-(3,4-dimethyl-benzylidene-hydrazinocarbonyl)-4-piperidin-1-yl-phenyl]-benzamide

The title compound 905 was produced in substantially the same manner as in Example F.

¹H-NMR (CDCl₃, 400 MHz): δ 0.99 (12H, t, J=7.1 Hz), 1.44 (2H, m), 1.57 (4H, m), 2.30 (6H, s), 2.50 (8H, m), 2.61 (8H, m), 3.00 (4H, m), 3.73 (2H, s), 7.02 (2H, m), 7.18 (1H, d, J=7.3 Hz), 7.42 (1H, dd, J=7.6 Hz, J=7.6 Hz), 7.51 (1H, m), 7.57 (1H, m), 7.67 (1H, s), 7.87 (1H, d, J=7.8 Hz), 7.97 (1H, s), 8.32 (2H, m), 11.14 (1H, s)

Mass spectrometric value (ESI-MS) 681 (M−1)

Compound 906 3-{[Bis-(2-diethylamino-ethyl)-amino]-methyl}-N-[2-(4-methyl-benzylidene-hydrazinocarbonyl)-4-piperidin-1-yl-phenyl]-benzamide

The title compound 906 was produced in substantially the same manner as in Example F.

¹H-NMR (CDCl₃, 400 MHz): δ 1.00 (12H, t, J=7.2 Hz), 1.25 (2H, m), 1.34 (4H, m), 2.37 (3H, s), 2.51 (8H, m), 2.62 (8H, m), 2.80 (4H, m), 3.75 (2H, s), 6.85 (1H, m), 6.97 (1H, m), 7.20 (2H, d, J=8.0 Hz), 7.43 (1H, d, J=7.6 Hz), 7.59 (1H, d, J=7.3 Hz), 7.75 (2H, d, J=7.8 Hz), 7.86 (1H, d, J=7.8 Hz), 8.00 (1H, s), 8.08 (1H, d, J=9.0 Hz), 8.59 (1H, s), 11.20 (1H, s)

Mass spectrometric value (ESI-MS) 667 (M−1)

Compound 907 3-{[Bis-(2-diethylamino-ethyl)-amino]-methyl}-N-[2-(4-fluoro-benzylidene-hydrazinocarbonyl)-4-piperidin-1-yl-phenyl]-benzamide

The title compound 907 was produced in substantially the same manner as in Example F.

¹H-NMR (CDCl₃, 400 MHz): δ 1.00 (12H, t, J=7.1 Hz), 1.26 (2H, m), 1.35 (4H, m), 2.51 (8H, m), 2.62 (8H, m), 2.81 (4H, m), 3.75 (2H, s), 6.85 (1H, d, J=9.0 Hz), 6.94 (1H, s), 7.10 (2H, dd, J=8.5 Hz, J=8.5 Hz), 7.44 (1H, d, J=7.6 Hz, J=7.6 Hz), 7.60 (1H, d, J=7.3 Hz), 7.85 (3H, m), 8.00 (1H, s), 8.03 (1H, d, J=9.0 Hz), 8.61 (1H, s), 11.14 (2H, m)

Mass spectrometric value (ESI-MS) 671 (M−1)

Compound 908 3-{[Bis-(2-diethylamino-ethyl)-amino]-methyl}-N-[2-(3-fluoro-benzylidene-hydrazinocarbonyl)-4-piperidin-1-yl-phenyl]-benzamide

The title compound 908 was produced in substantially the same manner as in Example F.

¹H-NMR (CDCl₃, 400 MHz): δ 1.00 (12H, t, J=7.1 Hz), 1.24 (2H, m), 1.33 (4H, m), 2.51 (8H, m), 2.62 (8H, m), 2.78 (4H, m), 3.76 (2H, s), 6.84 (1H, d, J=9.3 Hz), 6.91 (1H, s), 7.11 (1H, m), 7.34-7.48 (2H, m), 7.58-7.68 (3H, m), 7.87 (1H, d, J=7.8 Hz), 8.00 (2H, m), 8.61 (1H, s)

Mass spectrometric value (ESI-MS) 671 (M−1)

Compound 909 3-{[Bis-(2-diethylamino-ethyl)-amino]-methyl}-N-[2-(4-chloro-3-trifluoromethyl-benzylidene-hydrazinocarbonyl)-4-piperidin-1-yl-phenyl]-benzamide

The title compound 909 was produced in substantially the same manner as in Example F.

¹H-NMR (CDCl₃, 400 MHz): δ 1.00 (12H, t, J=7.1 Hz), 1.21 (2H, m), 1.30 (4H, m), 2.51 (8H, m), 2.62 (8H, m), 2.75 (4H, m), 3.77 (2H, s), 6.80 (1H, d, J=8.8 Hz), 6.88 (1H, s), 7.47 (1H, dd, J=7.7 Hz, J=7.7 Hz), 7.57 (1H, d, J=8.5 Hz), 7.64 (1H, d, J=7.6 Hz), 7.86 (1H, d, J=7.6 Hz), 7.91 (1H, d, J=9.0 Hz), 8.02 (1H, s), 8.08 (1H, d, J=8.0 Hz), 8.12 (1H, s), 8.67 (1H, s)

Mass spectrometric value (ESI-MS) 754 (M−1)

Compound 910 3-{[Bis-(2-diethylamino-ethyl)-amino]-methyl}-N-[2-(4-methoxy-benzylidene-hydrazinocarbonyl)-4-piperidin-1-yl-phenyl]-benzamide

The title compound 910 was produced in substantially the same manner as in Example F.

¹H-NMR (CDCl₃, 400 MHz): δ 1.00 (12H, t, J=7.1 Hz), 1.28 (2H, m), 1.38 (4H, m), 2.51 (8H, m), 2.61 (8H, m), 2.83 (4H, m), 3.75 (2H, s), 3.84 (3H, s), 6.85-7.00 (4H, m), 7.43 (1H, dd, J=7.6 Hz, J=7.6 Hz), 7.59 (1H, d, J=7.6 Hz), 7.79 (2H, d, J=8.5 Hz), 7.86 (1H, d, J=7.6 Hz), 7.99 (1H, s), 8.12 (1H, d, J=9.3 Hz), 8.51 (1H, s), 11.19 (1H, s)

Mass spectrometric value (ESI-MS) 682 (M−1)

Example G Compound 911 N-[2-(4-Chloro-3-trifluoromethyl-benzylidene-hydrazinocarbonyl)-4-dipropylamino-phenyl]-3-{[(2-diethylamino-ethyl)-methyl-amino]-methyl}-benzamide

5-Amino-2-nitro-benzoic acid methyl ester (compound A′) (800 mg) was dissolved in dry THF (15 ml). Propionaldehyde (compound D) (870 μA dissolved in a mixed liquid composed of 3 M sulfuric acid (4 ml) and THF (1 ml) was added to the solution at room temperature. Subsequently, sodium borohydride (231 mg) was added thereto at 0° C., and the mixture was stirred at room temperature for 3 hr. Thereafter, distilled water was added thereto, and the mixture was subjected to separatory extraction with chloroform. The organic layer was washed with saturated brine, was dried over sodium sulfate and was then concentrated. The residue was purified by column chromatography using a hexane-acetone system to give 2-nitro-5-propylamino-benzoic acid methyl ester as a useful intermediate (608 mg, yield 63%).

2-Nitro-5-propylamino-benzoic acid methyl ester (608 mg) produced by the above reaction was dissolved in dry THF (15 ml). Propionaldehyde (compound D) (461 μl) dissolved in a mixed liquid composed of 3 M sulfuric acid (2.1 ml) and THF (1 ml) was added to the solution at room temperature. Subsequently, sodium borohydride (145 mg) was added thereto at 0° C., and the mixture was stirred at room temperature for 3 hr. Thereafter, distilled water was added thereto, and the mixture was subjected to separatory extraction with chloroform. The organic layer was washed with saturated brine, was dried over sodium sulfate, and was then concentrated. The residue was purified by column chromatography using a hexane-acetone system to give 5-dipropylamino-2-nitro-benzoic acid methyl ester as a useful intermediate (149 mg, yield 21%).

5-Dipropylamino-2-nitro-benzoic acid methyl ester (467 mg) produced by the above reaction was dissolved in ethanol (5 ml), and 10% palladium-carbon (45 mg) was added to the solution. The air in the reaction system was then replaced by hydrogen, and the reaction solution was stirred at room temperature for 15 hr. After the completion of the reaction, the reaction solution was filtered through Celite. The filtrate was concentrated, and the residue was purified by column chromatography using a hexane-acetone system to give 2-amino-5-dipropylamino-benzoic acid methyl ester (compound A) (243 mg, yield 58%) as a useful intermediate.

2-Amino-5-dipropylamino-benzoic acid methyl ester (compound A) (243 mg) produced by the above reaction was dissolved in anhydrous methylene chloride (3.0 ml). Subsequently, pyridine (170 μl) and 3-(chloromethyl)benzoyl chloride (compound B) (166 μl) were added to the solution at 0° C., and the mixture was stirred at 0° C. for one hr. After the completion of the reaction, distilled water was added thereto, and the mixture was subjected to separatory extraction with chloroform. The organic layer was washed with saturated brine, was dried over sodium sulfate, and was then concentrated. The residue was purified by column chromatography using a hexane-acetone system to give 2-(3-chloromethyl-benzoylamino)-5-dipropylamino-benzoic acid methyl ester as a useful intermediate (280 mg, yield 64%).

2-(3-Chloromethyl-benzoylamino)-5-dipropylamino-benzoic acid methyl ester (280 mg) produced by the above reaction was dissolved in anhydrous methylene chloride (2.0 ml). Triethylamine (45 μl) and N,N-diethyl-N′-methylethylenediamine (compound B′) (50 μl) were added to the solution at room temperature, and the mixture was stirred at room temperature for 15 hr. After the completion of the reaction, water was added thereto at room temperature, and the mixture was subjected to separatory extraction with chloroform. The organic layer was washed with saturated brine, was dried over sodium sulfate, and was then concentrated, and the residue was purified by column chromatography using a hexane-acetone system to give 2-(3-{[(2-diethylamino-ethyl)-methyl-amino]-methyl}-benzoylamino)-5-dipropylamino-benzoic acid methyl ester as a useful intermediate (164 mg, yield 50%).

2-(3-{[(2-Diethylamino-ethyl)-methyl-amino]-methyl}-benzoylamino)-5-dipropylamino-benzoic acid methyl ester (164 mg) produced by the above reaction was dissolved in ethanol (5.0 ml). Hydrazine monohydrate (200 μl) was added to the solution, and the mixture was heated under reflux with stirring for 15 hr. After the completion of the reaction, water was added thereto at room temperature, and the mixture was subjected to separatory extraction with chloroform. The organic layer was washed with saturated brine, was dried over sodium sulfate, and was then concentrated. The residue was purified by column chromatography eluted with a chloroform-methanol system to give 3-{[(2-diethylamino-ethyl)-methyl-amino]-methyl}-N-(4-dipropylamino-2-hydrazinocarbonyl-phenyl)-benzamide as a hydrazine compound (96 mg, yield 58%).

3-{[(2-Diethylamino-ethyl)-methyl-amino]-methyl}-N-(4-dipropylamino-2-hydrazinocarbonyl-phenyl)-benzamide (47 mg) as the hydrazine compound produced by the above reaction was dissolved in anhydrous toluene (1.0 ml). 3-Trifluoromethyl-4-chlorobenzaldehyde (compound C) (40 μl) was added to the solution at room temperature, and the mixture was stirred at room temperature for 15 hr. After the completion of the reaction, the reaction product was purified by column chromatography eluted with a chloroform-methanol system to give the title compound 911 (57 mg, yield 88%).

¹H-NMR (CDCl₃, 400 MHz): δ 0.78 (6H, t, J=7.1 Hz), 1.04 (6H, t, J=7.1 Hz), 1.37 (4H, m), 2.26 (3H, s), 2.50-2.75 (8H, m), 2.85 (4H, m), 3.62 (2H, s), 6.49 (1H, d, J=7.8 Hz), 6.65 (1H, s), 7.44 (1H, dd, J=7.6 Hz, J=7.6 Hz), 7.55 (2H, m), 7.80-8.15 (5H, m), 8.63 (1H, s), 10.83 (1H, s)

Mass spectrometric value (ESI-MS) 685 (M−1)

Compound 912 3-{[(2-Diethylamino-ethyl)-methyl-amino]-methyl}-N-[4-dipropylamino-2-(4-methoxy-benzylidene-hydrazinocarbonyl)-phenyl]-benzamide

The title compound 912 was produced in substantially the same manner as in Example G.

¹H-NMR (CDCl₃, 400 MHz): δ 0.81 (6H, t, J=7.1 Hz), 1.05 (6H, t, J=7.1 Hz), 1.42 (4H, m), 2.24 (3H, s), 2.50-2.70 (8H, m), 2.95 (4H, m), 3.61 (2H, s), 3.83 (3H, s), 6.57 (1H, d, J=9.0 Hz), 6.72 (1H, s), 6.91 (2H, d, J=8.6 Hz), 7.41 (1H, dd, J=7.6 Hz, J=7.6 Hz), 7.52 (1H, d, J=7.3 Hz), 7.76 (2H, d, J=8.3 Hz), 7.85 (1H, d, J=7.6 Hz), 7.95 (1H, s), 8.05 (1H, d, J=9.0 Hz), 8.45 (1H, s), 10.93 (1H, s)

Mass spectrometric value (ESI-MS) 614 (M−1)

Compound 913 3-({2-[Bis-(2-hydroxy-ethyl)-amino]-ethylamino}-methyl)-N-[2-(3,4-dimethyl-benzylidene-hydrazinocarbonyl)-4-piperidin-1-yl-phenyl]-benzamide

The title compound 913 was produced in substantially the same manner as in Example F.

¹H-NMR (CDCl₃, 400 MHz): δ 1.41 (2H, m), 1.52 (4H, m), 2.25 (6H, s), 2.61 (4H, m), 2.71 (2H, m), 2.77 (2H, m), 2.97 (4H, m), 3.58 (4H, t, J=4.8 Hz), 3.92 (2H, s), 6.94 (1H, m), 7.07 (1H, s), 7.13 (1H, d, J=7.8 Hz), 7.40-7.55 (3H, m), 7.60 (1H, s), 7.93 (2H, m), 8.22 (1H, d, J=8.3 Hz), 8.38 (1H, s), 11.20 (1H, s)

Mass spectrometric value (ESI-MS) 613 (M−1)

Compound 914 3-({2-[Bis-(2-hydroxy-ethyl)-amino]-ethylamino}-methyl)-N-[2-(4-chloro-3-trifluoromethyl-benzylidene-hydrazinocarbonyl)-4-piperidin-1-yl-phenyl]-benzamide

The title compound 914 was produced in substantially the same manner as in Example F.

¹H-NMR (CDCl₃, 400 MHz): δ 1.44 (2H, m), 1.54 (4H, m), 2.60 (4H, m), 2.73 (2H, m), 2.86 (2H, m), 3.00 (4H, m), 3.56 (4H, m), 3.97 (2H, m), 6.90 (1H, m), 7.10 (1H, m), 7.73-7.55 (4H, m), 7.92 (2H, m), 8.02 (1H, m), 8.15 (1H, m), 8.60 (1H, s)

Mass spectrometric value (ESI-MS) 687 (M−1)

Compound 915 3-({2-[Bis-(2-hydroxy-ethyl)-amino]-ethylamino}-methyl)-N-[2-(4-methoxy-benzylidene-hydrazinocarbonyl)-4-piperidin-1-yl-phenyl]-benzamide

The title compound 915 was produced in substantially the same manner as in Example F.

¹H-NMR (CDCl₃, 400 MHz): δ 1.40 (2H, m), 1.51 (4H, m), 2.61 (4H, m), 2.70 (2H, m), 2.76 (2H, m), 2.96 (4H, m), 3.58 (4H, m), 3.81 (3H, s), 3.90 (2H, s), 6.88 (2H, d, J=8.1 Hz), 6.93 (1H, m), 7.07 (1H, s), 7.43 (1H, m), 7.50 (1H, m), 7.72 (2H, d, J=8.3 Hz), 7.92 (2H, m), 8.22 (1H, m), 8.36 (1H, s), 11.22 (1H, bs)

Mass spectrometric value (ESI-MS) 615 (M−1)

Compound 916 3-{[(2-Diethylamino-ethyl)-methyl-amino]-methyl}-N-[2-(3,4-dimethyl-benzylidene-hydrazinocarbonyl)-4-pyrrolidin-1-yl-phenyl]-benzamide

The title compound 916 was produced in substantially the same manner as in Example F.

¹H-NMR (CD₃OD, 400 MHz): δ 1.06 (6H, t, J=7.1 Hz), 1.99 (4H, m), 2.26 (9H, m), 2.58 (2H, m), 2.70 (4H, m), 2.82 (2H, m), 3.30 (4H, m), 3.63 (2H, s), 6.75 (1H, dd, J=9.2 Hz, J=2.8 Hz), 6.90 (1H, d, J=2.7 Hz), 7.14 (1H, d, J=7.8 Hz), 7.47 (2H, m), 7.54 (1H, d, J=7.8 Hz), 7.57 (1H, s), 7.85 (1H, d, J=7.8 Hz), 7.92 (1H, s), 8.24 (1H, d, J=9.0 Hz), 8.28 (1H, s)

Mass spectrometric value (ESI-MS) 581 (M−1)

Compound 917 N-[2-(4-Chloro-3-trifluoromethyl-benzylidene-hydrazinocarbonyl)-4-pyrrolidin-1-yl-phenyl]-3-{[(2-diethylamino-ethyl)-methyl-amino]-methyl}-benzamide

The title compound 917 was produced in substantially the same manner as in Example F.

¹H-NMR (CD₃OD, 400 MHz): δ 1.02 (6H, t, J=7.2 Hz), 1.99 (4H, m), 2.25 (3H, s), 2.57 (6H, m), 2.70 (2H, m), 3.30 (4H, m), 3.62 (2H, s), 6.74 (1H, dd, J=9.0 Hz, J=2.7 Hz), 6.89 (1H, d, J=2.7 Hz), 7.47 (1H, dd, J=7.6 Hz, J=7.6 Hz), 7.54 (1H, d, J=7.6 Hz), 7.60 (1H, d, J=8.3 Hz), 7.84 (1H, d, J=7.6 Hz), 7.93 (2H, m), 8.18 (1H, d, J=9.0 Hz), 8.23 (1H, m), 8.35 (1H, s)

Mass spectrometric value (ESI-MS) 655 (M−1)

Compound 918 3-{[(2-Diethylamino-ethyl)-methyl-amino]-methyl}-N-[2-(4-methoxy-benzylidene-hydrazinocarbonyl)-4-pyrrolidin-1-yl-phenyl]-benzamide

The title compound 918 was produced in substantially the same manner as in Example F.

¹H-NMR (CD₃OD, 400 MHz): δ 1.04 (6H, t, J=7.2 Hz), 2.00 (4H, m), 2.26 (3H, s), 2.52-2.68 (6H, m), 2.75 (2H, m), 3.31 (4H, m), 3.64 (2H, s), 3.81 (3H, s), 6.75 (1H, dd, J=9.0 Hz, J=2.7 Hz), 6.89 (1H, d, J=2.7 Hz), 6.93 (2H, d, J=8.8 Hz), 7.47 (1H, t, J=7.7 Hz), 7.54 (1H, d, J=7.3 Hz), 7.73 (2H, d, J=9.0 Hz), 7.85 (1H, m), 7.91 (1H, s), 8.25 (1H, d, J=9.0 Hz), 8.28 (1H, s)

Mass spectrometric value (ESI-MS) 583 (M−1)

Compound 919 N-[2-(3,4-Dimethyl-benzylidene-hydrazinocarbonyl)-4-pyrrolidin-1-yl-phenyl]-3-(2-hydroxy-ethylsulfanylmethyl)-benzamide

The title compound 919 was produced in substantially the same manner as in Example F.

¹H-NMR (CD₃OD, 400 MHz): δ 2.06 (4H, m), 2.29 (3H, s), 2.31 (3H, s), 2.57 (2H, t, J=7.0 Hz), 3.37 (4H, m), 3.68 (2H, t, J=6.8 Hz), 3.85 (2H, s), 6.81 (1H, d, J=8.1 Hz), 6.93 (1H, s), 7.02-7.23 (2H, m), 7.45-7.59 (2H, m), 7.64 (1H, s), 7.84 (1H, d, J=7.3 Hz), 7.90 (1H, s), 8.26 (2H, m)

Mass spectrometric value (ESI-MS) 529 (M−1)

Compound 920 N-[2-(4-Chloro-3-trifluoromethyl-benzylidene-hydrazinocarbonyl)-4-pyrrolidin-1-yl-phenyl]-3-(2-hydroxy-ethylsulfanylmethyl)-benzamide

The title compound 920 was produced in substantially the same manner as in Example F.

¹H-NMR (CD₃OD, 400 MHz): δ 2.07 (4H, m), 2.57 (2H, t, J=7.0 Hz), 3.38 (4H, m), 3.68 (2H, t, J=6.8 Hz), 3.85 (2H, s), 6.83 (1H, m), 6.94 (1H, m), 7.48 (1H, dd, J=7.7 Hz, J=7.7 Hz), 7.57 (1H, d, J=7.3 Hz), 7.67 (1H, d, J=8.3 Hz), 7.83 (1H, d, J=7.6 Hz), 7.90 (1H, s), 8.04 (1H, d, J=8.0 Hz), 8.22 (1H, d, J=9.0 Hz), 8.32 (1H, s), 8.36 (1H, s)

Mass spectrometric value (ESI-MS) 603 (M−1)

Compound 921 3-(2-Hydroxy-ethylsulfanylmethyl)-N-[2-(4-methoxy-benzylidene-hydrazinocarbonyl)-4-pyrrolidin-1-yl-phenyl]-benzamide

The title compound 921 was produced in substantially the same manner as in Example F.

¹H-NMR (CD₃OD, 400 MHz): δ 2.05 (4H, m), 2.57 (2H, t, J=7.0 Hz), 3.36 (4H, m), 3.68 (2H, t, J=6.8 Hz), 3.84 (5H, m), 6.81 (1H, d, J=8.8 Hz), 6.93 (1H, s), 6.97 (2H, d, J=9.0 Hz), 7.47 (1H, dd, J=7.7 Hz, J=7.7 Hz), 7.57 (1H, d, J=7.3 Hz), 7.77 (2H, d, J=8.8 Hz), 7.83 (1H, d, J=7.2 Hz), 7.90 (1H, s), 8.24 (1H, d, J=9.0 Hz), 8.27 (1H, s)

Mass spectrometric value (ESI-MS) 531 (M−1)

Compound 922 N-[2-(4-Chloro-3-trifluoromethyl-benzylidene-hydrazinocarbonyl)-4-(4-methyl-[1,4]diazepan-1-yl)-phenyl]-3-{[(2-diethylamino-ethyl)-methyl-amino]-methyl}-benzamide

The title compound 922 was produced in substantially the same manner as in Example F.

¹H-NMR (CDCl₃, 400 MHz): δ 1.03 (6H, t, J=7.1 Hz), 1.67 (2H, m), 2.20-2.80 (18H, m), 3.04 (2H, m), 3.11 (2H, m), 3.63 (2H, s), 6.57 (1H, d, J=8.6 Hz), 6.64 (1H, s), 7.46 (1H, m), 7.57 (2H, m), 7.78 (1H, d, J=7.8 Hz), 7.94 (1H, d, J=8.8 Hz), 8.00 (1H, s), 8.08 (1H, d, J=7.8 Hz), 8.13 (1H, s), 8.64 (1H, s), 10.87 (1H, s)

Mass spectrometric value (ESI-MS) 698, 699 (M−1)

Compound 923 N-{2-(4-Chloro-3-trifluoromethyl-benzylidene-hydrazinocarbonyl)-4-[4-(2-hydroxy-ethyl)-piperazin-1-yl]-phenyl}-3-(2-hydroxy-ethylsulfanylmethyl)-benzamide

The title compound 923 was produced in substantially the same manner as in Example F.

¹H-NMR (CD₃OD, 400 MHz): δ 2.57 (2H, t, J=7.0 Hz), 2.60 (2H, t, J=6.0 Hz), 2.72 (4H, m), 3.31 (4H, m), 3.68 (2H, t, J=7.0 Hz), 3.73 (2H, t, J=6.0 Hz), 3.85 (2H, s), 7.23 (1H, dd, J=9.0 Hz, J=2.7 Hz), 7.38 (1H, d, J=2.7 Hz), 7.48 (1H, dd, J=7.6 Hz, J=7.6 Hz), 7.58 (1H, d, J=7.8 Hz), 7.67 (1H, d, J=8.6 Hz), 7.84 (1H, d, J=7.6 Hz), 7.91 (1H, s), 8.02 (1H, d, J=8.6 Hz), 8.31 (1H, m), 8.37 (2H, m)

Mass spectrometric value (ESI-MS) 662 (M−1)

Compound 924 N-{2-(4-Chloro-3-trifluoromethyl-benzylidene-hydrazinocarbonyl)-4-[4-(2-hydroxy-ethyl)-piperazin-1-yl]-phenyl}-3-{[(2-diethylamino-ethyl)-methyl-amino]-methyl}-benzamide

The title compound 924 was produced in substantially the same manner as in Example F.

¹H-NMR (CD₃OD, 400 MHz): δ 1.01 (6H, t, J=7.2 Hz), 2.26 (3H, s), 2.58 (8H, m), 2.70 (6H, m), 3.32 (4H, m), 3.64 (2H, s), 3.73 (2H, t, J=5.9 Hz), 7.22 (1H, dd, J=9.0 Hz, J=2.7 Hz), 7.39 (1H, d, J=2.7 Hz), 7.49 (1H, dd, J=7.7 Hz, J=7.7 Hz), 7.57 (1H, d, J=7.6 Hz), 7.65 (1H, d, J=8.5 Hz), 7.87 (1H, m), 7.93 (1H, s), 7.99 (1H, d, J=8.3 Hz), 8.28 (1H, m), 8.36 (2H, m)

Mass spectrometric value (ESI-MS) 714 (M−1)

Compound 925 1-{3-(4-Chloro-3-trifluoromethyl-benzylidene-hydrazinocarbonyl)-4-[3-(2-hydroxy-ethylsulfanylmethyl)-benzoylamino]-phenyl}-piperidine-3-carboxylic acid

The title compound 925 was produced in substantially the same manner as in Example F.

¹H-NMR (DMSO-d₆, 400 MHz): δ 1.54-3.90 (15H, m), 7.24 (1H, m), 7.37 (1H, s), 7.54 (2H, m), 7.77 (1H, d, J=7.3 Hz), 7.82 (1H, d, J=8.3 Hz), 7.87 (1H, s), 8.05 (1H, d, J=8.1 Hz), 8.22 (2H, m), 8.54 (1H, s), 11.23 (1H, s), 12.34 (1H, s)

Mass spectrometric value (ESI-MS) 684 (M+23)

Compound 926 N-[2-(3,4-Dimethyl-benzylidene-hydrazinocarbonyl)-4-thiomorpholin-4-yl-phenyl]-3-(2-hydroxy-ethylsulfanylmethyl)-benzamide

The title compound 926 was produced in substantially the same manner as in Example F.

¹H-NMR (DMSO-d₆, 400 MHz): δ 2.27 (3H, s), 2.28 (3H, s), 2.73 (4H, m), 3.32-3.60 (8H, m), 3.85 (2H, s), 7.22 (2H, m), 7.31 (1H, d, J=2.9 Hz), 7.43-7.59 (4H, m), 7.77 (1H, d, J=7.1 Hz), 7.87 (1H, s), 8.30 (1H, m), 8.36 (1H, s), 11.38 (1H, s), 11.91 (1H, s)

Mass spectrometric value (ESI-MS) 561 (M−1)

Compound 927 N-[2-(4-Chloro-3-trifluoromethyl-benzylidene-hydrazinocarbonyl)-4-thiomorpholin-4-yl-phenyl]-3-(2-hydroxy-ethylsulfanylmethyl)-benzamide

The title compound 927 was produced in substantially the same manner as in Example F.

¹H-NMR (DMSO-d₆, 400 MHz): δ 2.72 (4H, m), 3.31 (2H, m), 3.56 (6H, m), 3.84 (2H, s), 4.79 (1H, m), 7.20 (1H, m), 7.29 (1H, m), 7.53 (2H, m), 7.77 (1H, d, J=7.6 Hz), 7.80 (1H, d, J=8.5 Hz), 7.86 (1H, s), 8.05 (1H, m), 8.21 (1H, s), 8.25 (1H, m), 8.48 (1H, s), 11.20 (1H, s), 12.21 (1H, s)

Mass spectrometric value (ESI-MS) 635 (M−1)

Compound 928 3-(2-Hydroxy-ethylsulfanylmethyl)-N-[2-(4-methoxy-benzylidene-hydrazinocarbonyl)-4-thiomorpholin-4-yl-phenyl]-benzamide

The title compound 928 was produced in substantially the same manner as in Example F.

¹H-NMR (DMSO-d₆, 400 MHz): δ 2.73 (4H, m), 3.35 (2H, m), 3.50-3.60 (6H, m), 3.82 (3H, s), 3.85 (2H, s), 7.03 (2H, d, J=8.8 Hz), 7.20 (1H, dd, J=9.1 Hz, J=2.8 Hz), 7.31 (1H, d, J=2.7 Hz), 7.54 (2H, m), 7.71 (2H, d, J=8.6 Hz), 7.77 (1H, d, J=7.3 Hz), 7.87 (1H, s), 8.31 (1H, d, J=9.3 Hz), 8.38 (1H, s), 11.42 (1H, s), 11.87 (1H, s)

Mass spectrometric value (ESI-MS) 563 (M−1)

Compound 929 N-[2-(4-Chloro-3-trifluoromethyl-benzylidene-hydrazinocarbonyl)-4-thiomorpholin-4-yl-phenyl]-3-{[(2-diethylamino-ethyl)-methyl-amino]-methyl}-benzamide

The title compound 929 was produced in substantially the same manner as in Example F.

¹H-NMR (CDCl₃, 400 MHz): δ 1.25 (6H, s), 2.28 (3H, s), 2.44 (4H, m), 2.56-2.76 (8H, m), 3.25 (4H, m), 3.65 (2H, s), 6.84 (1H, m), 7.00 (1H, s), 7.43-7.60 (3H, m), 7.88 (1H, m), 7.95-8.11 (4H, m), 8.60 (1H, s), 11.10 (1H, s)

Mass spectrometric value (ESI-MS) 687 (M−1)

Example H Compound 930 N-[5-Bromo-3-(4-methoxy-benzylidene-hydrazinocarbonyl)-thiophen-2-yl]-3-dimethylaminomethyl-benzamide

2-Amino-thiophene-3-carboxylic acid methyl ester (compound A) (3.0 g) was dissolved in anhydrous methylene chloride (100 ml). Subsequently, pyridine (2.4 ml) and 3-(chloromethyl)benzoyl chloride (compound B) (2.8 ml) were added to the solution at 0° C., and the mixture was stirred at 0° C. for one hr. After the completion of the reaction, distilled water was added thereto, and the mixture was subjected to separatory extraction with chloroform. The organic layer was washed with saturated brine, was dried over sodium sulfate and was then concentrated. The residue was purified by column chromatography using a hexane-acetone system to give 2-(3-chloromethyl-benzoylamino)-thiophene-3-carboxylic acid methyl ester as a useful intermediate (4.7 g, yield 100%).

2-(3-Chloromethyl-benzoylamino)-thiophene-3-carboxylic acid methyl ester (2.0 g) produced by the above reaction was dissolved in anhydrous methylene chloride (60 ml). Triethylamine (3 ml) and dimethylamine hydrochloride (compound B′) (1.1 g) were added to the solution at room temperature, and the mixture was stirred at room temperature for 15 hr. After the completion of the reaction, water was added thereto at room temperature, and the mixture was subjected to separatory extraction with chloroform. The organic layer was washed with saturated brine, was dried over sodium sulfate, and was then concentrated. The residue was purified by column chromatography using a hexane-acetone system to give 2-(3-dimethylaminomethyl-benzoylamino)-thiophene-3-carboxylic acid methyl ester as a useful intermediate (1.14 g, yield 52%).

2-(3-dimethylaminomethyl-benzoylamino)-thiophene-3-carboxylic acid methyl ester (1.14 g) produced by the above reaction was dissolved in monochlorobenzene. N-bromosuccinimide (877 mg) and 2,2′-azobisisobutyronitrile (81 mg) were added to the solution, and the mixture was stirred at 90° C. for 2 hr. After the completion of the reaction, the reaction solution was concentrated, and the residue was purified by column chromatography using a hexane-acetone system to give 5-bromo-2-(3-dimethylaminomethyl-benzoylamino)-thiophene-3-carboxylic acid methyl ester as a useful intermediate (706 mg, yield 54%).

5-Bromo-2-(3-dimethylaminomethyl-benzoylamino)-thiophene-3-carboxylic acid methyl ester (706 mg) produced by the above reaction was dissolved in ethanol (10 ml). Hydrazine monohydrate (1 ml) was added to the solution, and the mixture was stirred at room temperature for 15 hr. After the completion of the reaction, water was added thereto at room temperature, and the mixture was subjected to separatory extraction with chloroform. The organic layer was washed with saturated brine, was dried over sodium sulfate, and was then concentrated. The residue was purified by column chromatography eluted with a chloroform-methanol system to give N-(5-bromo-3-hydrazinocarbonyl-thiophen-2-yl)-3-dimethylaminomethyl-benzamide as a hydrazine compound (448 mg, yield 64%).

N-(5-bromo-3-hydrazinocarbonyl-thiophen-2-yl)-3-dimethylamino-methyl-benzamide (50 mg) as the hydrazine compound produced by the above reaction was dissolved in anhydrous toluene (1.0 ml). p-Methoxybenzaldehyde (compound C) (60 μl) was added to the solution at room temperature, and the mixture was stirred at room temperature for 15 hr. After the completion of the reaction, the reaction product was purified by column chromatography eluted with a chloroform-methanol system to give the title compound 930 (29 mg, yield 45%).

¹H-NMR (CDCl₃, 400 MHz): δ 2.22 (6H, s), 3.67 (2H, s), 3.78 (3H, s), 6.84 (2H, m), 7.42 (1H, dd, J=7.6 Hz, J=7.6 Hz), 7.54-7.61 (3H, m), 7.89 (1H, d, J=7.6 Hz), 7.93 (1H, s), 8.22 (1H, s), 9.87 (1H, bs), 12.93 (1H, bs)

Mass spectrometric value (ESI-MS) 515 (M−1)

Compound 931 3-{[(2-Diethylamino-ethyl)-methyl-amino]-methyl}-N-[2-(4-methoxy-benzylidene-hydrazinocarbonyl)-4-(4-methyl-[1,4]diazepan-1-yl)-phenyl]-benzamide

The title compound 931 was produced in substantially the same manner as in Example F.

¹H-NMR (CDCl₃, 400 MHz): δ 1.03 (6H, t, J=7.2 Hz), 1.73 (2H, m), 2.24 (5H, m), 2.37 (2H, m), 2.44-2.60 (9H, m), 2.65 (2H, m), 3.12 (2H, m), 3.20 (2H, m), 3.61 (2H, s), 3.84 (3H, s), 6.62 (1H, m), 6.69-6.78 (2H, m), 6.92 (2H, d, J=8.5 Hz), 7.41 (1H, dd, J=7.6 Hz, J=7.6 Hz), 7.52 (1H, d, J=7.6 Hz), 7.80 (2H, d, J=8.1 Hz), 7.96 (1H, s), 8.08 (1H, d, J=9.0 Hz), 8.49 (1H, s), 11.01 (1H, s)

Mass spectrometric value (ESI-MS) 626 (M−1)

Compound 932 3-[(4-Chloro-3-trifluoromethyl-benzylidene)-amino]-2-[3-(2-hydroxy-ethylsulfanylmethyl)-phenyl]-6-(4-methyl-[1,4]diazepan-1-yl)-3H-quinazolin-4-one

The title compound 932 was produced in substantially the same manner as in Example F.

¹H-NMR (CDCl₃, 400 MHz): δ 2.10 (2H, m), 2.42 (3H, s), 2.55-2.68 (4H, m), 2.80 (2H, m), 3.58-3.84 (8H, m), 7.23 (1H, m), 7.34-7.44 (3H, m), 7.54 (2H, m), 7.68 (2H, m), 7.76 (1H, m), 7.95 (1H, d, J=1.7 Hz), 9.36 (1H, s)

Mass spectrometric value (ESI-MS) 652 (M+23)

Compound 933 2-(3-{[(2-Diethylamino-ethyl)-methyl-amino]-methyl}-phenyl)-3-[(4-methoxy-benzylidene)-amino]-6-(4-methyl-[1,4]diazepan-1-yl)-3H-quinazolin-4-one

The title compound 933 was produced in substantially the same manner as in Example F.

¹H-NMR (CDCl₃, 400 MHz): δ 0.99 (6H, t, J=7.2 Hz), 2.06 (2H, m), 2.11 (3H, s), 2.39 (3H, s), 2.45-2.60 (10H, m), 2.76 (2H, m), 3.51 (2H, s), 3.62 (2H, t, J=6.3 Hz), 3.70 (2H, m), 3.84 (3H, s), 6.90 (2H, d, J=8.8 Hz), 7.22 (1H, dd, J=9.0 Hz, J=3.2 Hz), 7.35 (1H, m), 7.44 (1H, d, J=3.2 Hz), 7.57 (1H, m), 7.60-7.70 (4H, m), 8.88 (1H, s)

Mass spectrometric value (ESI-MS) 632 (M+23)

Compound 934 1-{3-(3,4-Dimethyl-benzylidene-hydrazinocarbonyl)-4-[3-(2-hydroxy-ethylsulfanylmethyl)-benzoylamino]-phenyl}-piperidine-3-carboxylic acid

The title compound 934 was produced in substantially the same manner as in Example F.

¹H-NMR (DMSO-d₆, 400 MHz): δ 1.50-3.88 (21H, m), 7.14-7.60 (7H, m), 7.77 (1H, d, J=7.3 Hz), 7.87 (1H, s), 8.32 (1H, d, J=9.0 Hz), 8.40 (1H, s), 11.44 (1H, s), 12.01 (1H, s)

Mass spectrometric value (ESI-MS) 609 (M+23)

Example I Compound 935 N-[2-(3,4-Dimethyl-benzylidene-hydrazinocarbonyl)-4-piperidin-1-yl-phenyl]-3,4-dimethoxy-benzamide

5-Chloro-2-nitro-benzoic acid (compound A′) (10.0 g) was dissolved in ethanol (100 ml). Thionyl chloride (20 ml) was added dropwise to the solution at 0° C., and the mixture was then heated under reflux with stirring for 48 hr. After the completion of the reaction, the reaction solution was concentrated under the reduced pressure. Distilled water was added to the residue, and the mixture was neutralized with a saturated aqueous sodium hydrogencarbonate solution under ice cooling. The cooled solution was subjected to separatory extraction with ethyl acetate. The organic layer was dried over sodium sulfate and was then concentrated under the reduced pressure. The residue was purified by column chromatography eluted with a chloroform-methanol system to give 5-chloro-2-nitro-benzoic acid ethyl ester as a useful intermediate (11.0 g, yield 97%).

5-Chloro-2-nitro-benzoic acid ethyl ester (3.1 g) produced by the above production process was dissolved in N,N-dimethylformamide (30 ml). Potassium carbonate (3.8 g) and piperidine (compound D) (2.8 ml) were added to the solution at room temperature, and the mixture was then heated under reflux with stirring for 12 hr. After the completion of the reaction, distilled water was added thereto at room temperature, and the mixture was subjected to separatory extraction with ethyl acetate. The organic layer was washed with saturated brine, was dried over sodium sulfate, and was then concentrated under the reduced pressure to give crude 2-nitro-5-piperidin-1-yl-benzoic acid ethyl ester (3.81 g, crude yield 100%).

Subsequently, the crude 2-nitro-5-piperidin-1-yl-benzoic acid ethyl ester (3.8 g) was dissolved in methanol (35 ml). Platinum oxide (300 mg) was added to the solution at room temperature, the air in the reaction system was replaced by hydrogen, and the mixture was then stirred for 12 hr. After the completion of the reaction, the atmosphere in the reaction system was replaced by nitrogen, and the reaction solution was then filtered through Celite to remove platinum oxide and was then concentrated under the reduced pressure to give crude 2-amino-5-piperidin-1-yl-benzoic acid ethyl ester (compound A) as a useful intermediate (3.4 g, crude yield 100%).

Subsequently, crude 2-amino-5-piperidin-1-yl-benzoic acid ethyl ester (compound A) (1.3 g) was dissolved in anhydrous methylene chloride (100 ml). Triethylamine (5.6 ml) and 3,4-dimethoxy-benzoyl chloride (compound B) (1.8 g) were added at 0° C., and the mixture was stirred at room temperature for 24 hr. After the completion of the reaction, distilled water was added thereto at room temperature, and the mixture was subjected to separatory extraction with chloroform. The organic layer was washed with saturated brine, was dried over sodium sulfate, and was then concentrated under the reduced pressure. The residue was purified by column chromatography eluted with a hexane-chloroform system to give 2-(3,4-dimethoxy-benzoylamino)-5-piperidin-1-yl-benzoic acid ethyl ester (960 mg, yield 52%).

2-(3,4-Dimethoxy-benzoylamino)-5-piperidin-1-yl-benzoic acid ethyl ester (380 mg) produced by the above process was dissolved in ethanol (10 ml). Hydrazine monohydrate (3 ml) was added dropwise to the solution at room temperature, and the mixture was stirred at 90° C. for 1.5 hr. After the completion of the reaction, the reaction solution was allowed to stand for cooling, and the precipitated crystals were filtered through Kiriyama Rohto to give N-(2-hydrazinocarbonyl-4-piperidin-1-yl-phenyl)-3,4-dimethoxy-benzamide as a useful intermediate (270 mg, yield 71%).

Subsequently, N-(2-hydrazinocarbonyl-4-piperidin-1-yl-phenyl)-3,4-dimethoxy-benzamide (56 mg) produced by the above process was dissolved in anhydrous toluene (5 ml). 3,4-Dimethylbenzaldehyde (compound C) (40 mg) and a catalytic amount of acetic acid were added dropwise to the solution at room temperature, and the mixture was stirred at 90° C. for 16 hr. After the completion of the reaction, distilled water was added thereto at room temperature, and the mixture was subjected to separatory extraction with chloroform. The organic layer was washed with saturated brine, was dried over sodium sulfate, and was then concentrated under the reduced pressure. The residue was purified by column chromatography eluted with a chloroform-methanol system to give the title compound 935 (74 mg, yield 96%).

¹H-NMR (CD₃OD, 400 MHz): δ 8.32 (1H, d, J=9.2 Hz), 8.28 (1H, s), 7.63 (1H, s), 7.59 (1H, dd, J=2.2 Hz, J=8.3 Hz), 7.54 (1H, d, J=1.9 Hz), 7.52 (1H, d, J=7.8 Hz), 7.36 (1H, d, J=2.7 Hz), 7.17-7.24 (2H, m), 7.06 (1H, d, J=8.6 Hz), 3.92 (3H, s), 3.90 (3H, s), 3.20-3.25 (4H, m), 2.30 (3H, s), 2.29 (3H, s), 1.70-1.80 (4H, m), 1.57-1.66 (2H, m)

Mass spectrometric value (ESI-MS) 513, 514 (M−1) 537, 538 (M+23)

Compound 936 3,4-Dimethoxy-N-[4-piperidin-1-yl-2-(pyridin-3-ylmethylene-hydrazinocarbonyl)-phenyl]-benzamide

The title compound 936 was produced in substantially the same manner as in Example I.

¹H-NMR (CD₃OD, 400 MHz): δ 8.89 (1H, s), 8.55-8.60 (1H, m), 8.39 (1H, s), 8.34-8.39 (1H, m), 8.28 (1H, d, J=9.0 Hz), 7.48-7.61 (3H, m), 7.37 (1H, d, J=2.9 Hz), 7.22 (1H, dd, J=2.9 Hz, J=9.3 Hz), 7.06 (1H, d, J=8.3 Hz), 3.91 (3H, s), 3.90 (3H, s), 3.20-3.25 (4H, m), 1.70-1.80 (4H, m), 1.57-1.66 (2H, m)

Mass spectrometric value (ESI-MS) 486 (M−1)

Compound 937 N-[2-(1H-Imidazol-2-ylmethylene-hydrazinocarbonyl)-4-piperidin-1-yl-phenyl]-3,4-dimethoxy-benzamide

The title compound 937 was produced in substantially the same manner as in Example I.

¹H-NMR (CD₃OD, 400 MHz): δ 8.34 (1H, d, J=9.0 Hz), 7.03-7.62 (8H, m), 3.93 (3H, s), 3.90 (3H, s), 3.15-3.19 (4H, m), 1.55-1.84 (6H, m)

Mass spectrometric value (ESI-MS) 475 (M−1)

Compound 938 N-[2-(4-Hydroxy-3-methoxy-benzylidene-hydrazinocarbonyl)-4-piperidin-1-yl-phenyl]-3,4-dimethoxy-benzamide

The title compound 938 was produced in substantially the same manner as in Example I.

¹H-NMR (CD₃OD, 400 MHz): δ 8.32 (1H, d, J=9.3 Hz), 8.24 (1H, s), 7.71 (1H, d, J=1.7 Hz), 7.59 (1H, dd, J=1.9 Hz, J=8.3 Hz), 7.56 (1H, d, J=2.0 Hz), 7.36 (1H, d, J=2.9 Hz), 7.22 (1H, dd, J=2.9 Hz, J=9.3 Hz), 7.05-7.11 (2H, m), 6.82 (1H, d, J=8.0 Hz), 3.94 (3H, s), 3.92 (3H, s), 3.90 (3H, s), 3.21-3.25 (4H, m), 1.71-1.80 (4H, m), 1.58-1.67 (2H, m)

Mass spectrometric value (ESI-MS) 529, 531, 532 (M−1) 555 (M+23)

Compound 939 N-[2-(3,4-Dimethyl-benzylidene-hydrazinocarbonyl)-4-morpholin-4-yl-phenyl]-3,4-dimethoxy-benzamide

The title compound 939 was produced in substantially the same manner as in Example I.

¹H-NMR (CD₃OD, 400 MHz): δ 8.37 (1H, d, J=9.3 Hz), 8.28 (1H, s), 7.65 (1H, s), 7.60 (1H, dd, J=2.2 Hz, J=8.3 Hz), 7.56 (1H, d, J=2.2 Hz), 7.50-7.55 (1H, m), 7.37 (1H, d, J=2.7 Hz), 7.21-7.26 (1H, m), 7.20 (1H, d, J=7.8 Hz), 7.08 (1H, d, J=8.3 Hz), 3.92 (3H, s), 3.91 (3H, s), 3.85-3.89 (4H, m), 3.20-3.29 (4H, m), 2.32 (3H, s), 2.30 (3H, s)

Mass spectrometric value (ESI-MS) 515 (M−1)

Compound 940 N-[2-(4-Hydroxy-3-methoxy-benzylidene-hydrazinocarbonyl)-4-morpholin-4-yl-phenyl]-3,4-dimethoxy-benzamide

The title compound 940 was produced in substantially the same manner as in Example I.

¹H-NMR (CDCL₃, 400 MHz): δ 11.6 (1H, bs), 8.27-8.40 (2H, m), 7.55-7.62 (2H, m), 7.47-7.53 (1H, m), 7.40-7.44 (1H, m), 6.88-7.16 (4H, m), 3.98 (3H, s), 3.97 (3H, s), 3.94 (3H, s), 3.60-3.72 (4H, m), 2.97-3.05 (4H, m)

Mass spectrometric value (ESI-MS) 533, 534, 535 (M−1) 1067 (2M−1)

Compound 941 3,4-Dimethoxy-N-[2-(4-methoxy-benzylidene-hydrazinocarbonyl)-4-morpholin-4-yl-phenyl]-benzamide

The title compound 941 was produced in substantially the same manner as in Example I.

¹H-NMR (CD₃OD, 400 MHz): δ 8.28-8.32 (1H, m), 7.83-7.89 (1H, m), 7.73-7.82 (2H, m), 7.53-7.66 (3H, m), 7.20-7.30 (1H, m), 7.05-7.12 (1H, m), 6.96-7.04 (2H, m), 3.83-3.95 (13H, m), 3.29-3.35 (4H, m)

Mass spectrometric value (ESI-MS) 519, 520 (M+1)

Example J Compound 942 3-{[Bis-(2-hydroxy-propyl)-amino]-methyl}-N-[2-(4-chloro-3-trifluoromethyl-benzylidene-hydrazinocarbonyl)-4-piperidin-1-yl-phenyl]-benzamide

5-Chloro-2-nitro-benzoic acid (compound A′) (10.0 g) was dissolved in ethanol (100 ml). Thionyl chloride (20 ml) was added dropwise to the solution at 0° C., and the mixture was then heated under reflux with stirring for 48 hr. After the completion of the reaction, the reaction solution was concentrated under the reduced pressure. Distilled water was added to the residue, and the mixture was neutralized with a saturated aqueous sodium hydrogencarbonate solution under ice cooling, and was then subjected to separatory extraction with ethyl acetate. The organic layer was dried over sodium sulfate and was then concentrated under the reduced pressure. The residue was purified by column chromatography eluted with a chloroform-methanol system to give 5-chloro-2-nitro-benzoic acid ethyl ester as a useful intermediate (11.0 g, yield 97%).

5-Chloro-2-nitro-benzoic acid ethyl ester (3.1 g) produced by the above process was dissolved in N,N-dimethylformamide (30 ml), potassium carbonate (3.8 g) and piperidine (compound D) (2.8 ml) were added to the solution at room temperature, and was then heated under reflux with stirring for 12 hr. After the completion of the reaction, distilled water was added thereto at room temperature, and the mixture was subjected to separatory extraction with ethyl acetate. The organic layer was washed with saturated brine, was dried over sodium sulfate, and was then concentrated under the reduced pressure to give crude 2-nitro-5-piperidin-1-yl-benzoic acid ethyl ester (3.8 g, crude yield 100%).

Subsequently, crude 2-nitro-5-piperidin-1-yl-benzoic acid ethyl ester (3.8 g) was dissolved in methanol (35 ml), and platinum oxide (300 mg) was added to the solution at room temperature. The air in the reaction system was replaced by hydrogen, and the mixture was then stirred for 12 hr. After the completion of the reaction, the atmosphere in the reaction system was replaced by nitrogen, and the reaction solution was then filtered through Celite to remove platinum oxide, and was then concentrated under the reduced pressure to give crude 2-amino-5-piperidin-1-yl-benzoic acid ethyl ester (compound A) as a useful intermediate (3.4 g, crude yield 100%).

2-Amino-5-piperidin-1-yl-benzoic acid ethyl ester (compound A) (1.6 g) synthesized by the above process was dissolved in anhydrous methylene chloride (20 ml). Pyridine (1.0 ml) and 3-(chloromethyl)benzoyl chloride (compound B) (1.2 ml) were added dropwise to the solution at 0° C., and the mixture was then stirred at room temperature for one hr. After the completion of the reaction, the reaction solution was concentrated under the reduced pressure. Distilled water was added to the residue, and the mixture was subjected to separatory extraction with ethyl acetate. The organic layer was dried over sodium sulfate and was then concentrated under the reduced pressure. The residue was purified by column chromatography eluted with a chloroform-methanol system to give 2-(3-chloromethyl-benzoylamino)-5-piperidin-1-yl-benzoic acid ethyl ester as a useful intermediate (1.7 g, yield 63%).

2-(3-Chloromethyl-benzoylamino)-5-piperidin-1-yl-benzoic acid ethyl ester (200 mg) produced by the above reaction was dissolved in anhydrous methylene chloride (2 ml). Triethylamine (150 μl) and diisopropanolamine (compound B′) (150 mg) were added to the solution at room temperature, and the mixture was then stirred at that temperature for 36 hr. After the completion of the reaction, distilled water was added thereto at room temperature, and the mixture was subjected to separatory extraction with chloroform. The organic layer was washed with saturated brine, was dried over sodium sulfate, and was then concentrated under the reduced pressure. The residue was purified by column chromatography eluted with a chloroform-methanol system to give 2-(3-{[bis-(2-hydroxy-propyl)-amino]-methyl}-benzoylamino)-5-piperidin-1-yl-benzoic acid ethyl ester as a useful intermediate (200 mg, yield 82%).

Subsequently, 2-(3-{[bis-(2-hydroxy-propyl)amino]-methyl}-benzoylamino)-5-piperidin-1-yl-benzoic acid ethyl ester (200 mg) was dissolved in ethanol (2 ml). Hydrazine monohydrate (200 μl) was added dropwise to the solution at room temperature, and the mixture was then stirred at that temperature for 12 hr. After the completion of the reaction, the reaction solution was concentrated under the reduced pressure. The residue was purified by column chromatography eluted with a chloroform-methanol system to give 3-{[bis-(2-hydroxy-propyl)-amino]-methyl}-N-(2-hydrazinocarbonyl-4-piperidin-1-yl-phenyl)benzamide as a useful intermediate (200 mg, yield 100%).

3-{[Bis-(2-hydroxy-propyl)-amino]-methyl}-N-(2-hydrazino-carbonyl-4-piperidin-1-ylphenyl)benzamide (53 mg) produced by the above process was dissolved in anhydrous toluene (5 ml). 4-Chloro-3-(trifluoromethyl)benzaldehyde (compound C) (69 mg) and a catalytic amount of acetic acid were added dropwise to the solution at room temperature, and the mixture was then stirred at 90° C. for 3 hr. After the completion of the reaction, the reaction solution was allowed to stand for cooling, and the resultant crystals were collected by Kiriyama Rohto to give the title compound 942 (15 mg, yield 20%). The filtrate obtained by the filtration through Kiriyama Rohto was concentrated under the reduced pressure, and the residue was purified by column chromatography eluted with a chloroform-methanol system to again give the title compound 942 (37 mg, yield 50%) (final step: total yield 70%).

¹H-NMR (CD₃OD, 400 MHz): δ 8.31-8.38 (3H, m), 8.00-8.07 (2H, m), 7.86 (1H, d, J=8.0 Hz), 7.67 (1H, d, J=8.6 Hz), 7.58 (1H, d, J=7.8 Hz), 7.48 (1H, dd, J=7.6 Hz, J=7.6 Hz), 7.38 (1H, d, J=2.7 Hz), 7.23 (1H, dd, J=2.7 Hz, J=9.0 Hz), 3.83-3.95 (4H, m), 3.20-3.25 (4H, m), 2.38-2.55 (4H, m), 1.70-1.78 (4H, m), 1.58-1.66 (2H, m), 1.07 (3H, s), 1.06 (3H, s)

Mass spectrometric value (ESI-MS) 672, 674 (M−1)

Example K Compound 943 3-{[Bis-(2-hydroxy-propyl)-amino]-methyl}-N-[4-(2-diethylamino-ethoxy)-2-(3,4-dimethyl-benzylidene-hydrazinocarbonyl)-phenyl]-benzamide

3-{[Bis-(2-hydroxy-propyl)-amino]-methyl}-N-[2-(3,4-dimethyl-benzylidene-hydrazinocarbonyl)-4-hydroxyphenyl]-benzamide (45 mg) produced in substantially the same manner as in Example 8 was dissolved in N,N-dimethylformamide (10 ml). 60% Sodium hydride (4.0 mg) was added to the solution at room temperature, and the mixture was stirred at that temperature for 10 min. Subsequently, (2-bromoethyl)diethylamine hydrobromide (44 mg) was added thereto, and the mixture was stirred for 12 hr. After the completion of the reaction, distilled water was added thereto, and the mixture was subjected to separatory extraction with ethyl acetate. The organic layer was washed with saturated brine and was dried over sodium sulfate. The organic layer was concentrated under the reduced pressure, and the residue was purified by column chromatography eluted with a chloroform system to give the title compound 943 (7 mg, yield 13%).

¹H-NMR (CDCL₃, 400 MHz): δ 10.02 (1H, bs), 8.20-8.25 (1H, m), 7.75-8.00 (3H, m), 7.35-7.50 (2H, m), 7.30 (1H, s), 7.23 (1H, s), 6.96-7.10 (3H, m), 4.25-4.45 (2H, m), 3.70-4.00 (4H, m), 2.30-2.80 (10H, m), 2.20-2.30 (6H, m), 1.00-1.20 (12H, m)

Mass spectrometric value (ESI-MS) 630 (M−1) 654 (M+23)

Example L Compound 944 3-{[Bis-(2-hydroxy-propyl)-amino]-methyl}-N-[2-(3,4-dimethyl-benzylidene-hydrazinocarbonyl)-4-(2-oxo-pyrrolidin-1-yl)-phenyl]-benzamide

5-Amino-2-nitro-benzoic acid (compound A′) (910 mg) was dissolved in methanol (50 ml). Thionyl chloride (0.74 ml) was added dropwise to the solution on an ice bath, and a reaction was allowed to proceed under reflux with heating for 12 hr. After the completion of the reaction, the reaction solution was allowed to stand for cooling to room temperature and was then concentrated under the reduced pressure. The residue was purified by column chromatography eluted with a chloroform-methanol system to give 5-amino-2-nitro-benzoic acid methyl ester (410 mg, yield 42%).

Subsequently, 5-amino-2-nitro-benzoic acid methyl ester (750 mg) was dissolved in anhydrous methylene chloride (30 ml). Pyridine (360 mg: dissolved in 2 ml of anhydrous methylene chloride) and 4-chloro-butyryl chloride (compound D) (630 mg: dissolved in 2 ml of anhydrous methylene chloride) were added dropwise at room temperature, and the mixture was then stirred at that temperature for 12 hr. After the completion of the reaction, distilled water was added thereto at room temperature, and the mixture was subjected to separatory extraction with chloroform. The organic layer was washed with saturated brine, was dried over sodium sulfate, and was then concentrated under the reduced pressure. The residue was purified by column chromatography eluted with a chloroform-methanol system to give 5-(4-chloro-butyrylamino)-2-nitro-benzoic acid methyl ester as a useful intermediate (1.2 g, yield 100%).

Subsequently, 5-(4-chloro-butyrylamino)-2-nitro-benzoic acid methyl ester (50 mg) was dissolved in N,N-dimethylformamide (5 ml). Morpholine (70 mg) and potassium carbonate (44 mg) were added to the solution at room temperature, and the mixture was stirred at room temperature for 3 hr. After the completion of the reaction, distilled water was added thereto at room temperature, and the mixture was subjected to separatory extraction with chloroform. The organic layer was washed with saturated brine, was dried over sodium sulfate, and was then concentrated under the reduced pressure. The residue was purified by column chromatography eluted with a chloroform-methanol system to give 2-nitro-5-(2-oxo-pyrrolidin-1-yl)-benzoic acid methyl ester (45 mg, yield 100%).

2-Nitro-5-(2-oxo-pyrrolidin-1-yl)-benzoic acid methyl ester (24 mg) was dissolved in ethanol (5 ml), and 10% palladium-carbon (3 mg) was added to the solution at room temperature. The air in the reaction system was replaced by hydrogen, and the reaction solution was then stirred at that temperature for 4 hr. After the completion of the reaction, the reaction solution was filtered through Celite to remove 10% palladium-carbon and was then concentrated under the reduced pressure. The residue was purified by column chromatography eluted with a chloroform-methanol system to give 2-amino-5-(2-oxo-pyrrolidin-1-yl)benzoic acid methyl ester (compound A) (10 mg, yield 83%).

2-Amino-5-(2-oxo-pyrrolidin-1-yl)benzoic acid methyl ester (compound A) (10 mg) produced by the above process was dissolved in anhydrous methylene chloride. Pyridine (5 mg: dissolved in 1 ml of anhydrous methylene chloride) and 3-(chloromethyl)benzoyl chloride (compound B) (11 mg: dissolved in 1 ml of anhydrous methylene chloride) were added dropwise to the solution at 0° C., and the mixture was stirred at room temperature for 12 hr. After the completion of the reaction, distilled water was added thereto at room temperature, and the mixture was subjected to separatory extraction with chloroform. The organic layer was washed with saturated brine, was dried over sodium sulfate, and was then concentrated under the reduced pressure. The residue was purified by column chromatography eluted with a chloroform-methanol system to give 2-(3-chloromethyl-benzoylamino)-5-(2-oxo-pyrrolidin-1-yl)benzoic acid methyl ester (14 mg, yield 93%).

Subsequently, 2-(3-chloromethyl-benzoylamino)-5-(2-oxo-pyrrolidin-1-yl)benzoic acid methyl ester (14 mg) was dissolved in anhydrous methylene chloride (5 ml). Triethylamine (7 mg: dissolved in 2 ml of anhydrous methylene chloride) and diisopropanolamine (compound B′) (10 mg: dissolved in 2 ml of anhydrous methylene chloride) were added dropwise to the solution at 0° C., and the mixture was stirred at room temperature for 24 hr. After the completion of the reaction, distilled water was added thereto at room temperature, and the mixture was subjected to separatory extraction with chloroform. The organic layer was washed with saturated brine, was dried over sodium sulfate, and was then concentrated under the reduced pressure. The residue was purified by column chromatography eluted with a chloroform-methanol system to give 2-(3-{[bis-(2-hydroxy-propyl)-amino]-methyl}-benzoylamino)-5-(2-oxo-pyrrolidin-1-yl)-benzoic acid methyl ester (8.0 mg, yield 47%).

2-(3-{[Bis-(2-hydroxy-propyl)-amino]-methyl}-benzoylamino)-5-(2-oxo-pyrrolidin-1-yl)-benzoic acid methyl ester (8.0 mg) produced by the above reaction was dissolved in ethanol (5 ml). Hydrazine monohydrate (1 ml) was added dropwise to the solution at room temperature, and the mixture was stirred at that temperature for one hr. After the completion of the reaction, the reaction solution was concentrated under the reduced pressure, and the residue was purified by column chromatography eluted with a chloroform-methanol system to give 3-{[bis-(2-hydroxy-propyl)-amino]-methyl}-N-[2-hydrazinocarbonyl-4-(2-oxo-pyrrolidin-1-yl)-phenyl]-benzamide (8.0 mg, yield 100%).

Subsequently, 3-{[bis-(2-hydroxy-propyl)-amino]-methyl}-N-[2-hydrazinocarbonyl-4-(2-oxo-pyrrolidin-1-yl)-phenyl]-benzamide (8.0 mg) produced by the above reaction was dissolved in anhydrous toluene (5 ml). 3,4-Dimethylbenzaldehyde (compound C) (4.6 mg: dissolved in 2 ml of anhydrous toluene) and a catalytic amount of acetic acid were added dropwise to the solution at room temperature, and the mixture was stirred at that temperature for 4 hr. After the completion of the reaction, the reaction solution was neutralized with a saturated aqueous sodium hydrogencarbonate solution, and was then subjected to separatory extraction with ethyl acetate. The organic layer was washed with saturated brine, was dried over sodium sulfate, and was then concentrated under the reduced pressure. The residue was purified by column chromatography eluted with a chloroform-methanol system to give the title compound 944 (6.5 mg, yield 65%).

¹H-NMR (CDCL₃, 400 MHz): δ 12.11 (1H, d, J=8.3 Hz), 10.88 (1H, d, J=9.8 Hz), 8.74 (1H, dd, J=17.1 Hz, J=9.0 Hz), 8.20-8.30 (3H, m), 7.95-8.05 (1H, m), 7.28-7.60 (5H, m), 7.08 (1H, dd, J=3.4 Hz, J=8.0 Hz), 3.75-4.10 (5H, m), 2.40-2.61 (5H, m), 2.25 (3H, s), 2.23 (3H, s), 1.95-2.15 (2H, m), 1.25 (2H, s), 1.11 (6H, d, J=6.4 Hz)

Mass spectrometric value (ESI-MS) 598 (M−1) 622 (M+23)

Compound 945 3-{[Bis-(2-hydroxy-propyl)-amino]-methyl}-N-[2-(4-chloro-3-trifluoromethyl-benzylidene-hydrazinocarbonyl)-4-(2-oxo-pyrrolidin-1-yl)-phenyl]-benzamide

The title compound 945 was produced in substantially the same manner as in Example L.

¹H-NMR (CDCL₃, 400 MHz): δ 12.33 (1H, d, J=9.0 Hz,), 11.94 (1H, bs), 8.71 (1H, dd, J=9.0 Hz, J=9.0 Hz), 8.07-8.40 (3H, m), 8.11 (1H, d, J=21.0 Hz), 7.99 (1H, d, J=7.3 Hz), 7.78 (1H, dd, J=8.3 Hz, J=29.0 Hz), 7.20-7.50 (4H, m), 3.55-4.20 (6H, m), 2.45-2.74 (4H, m), 2.25-2.42 (2H, m), 1.78-1.87 (2H, m), 1.50-1.72 (6H, m)

Mass spectrometric value (ESI-MS) 672 (M−1)

Compound 946 3-{[Bis-(2-hydroxy-propyl)-amino]-methyl}-N-[2-(4-methoxy-benzylidene-hydrazinocarbonyl)-4-(2-oxo-pyrrolidin-1-yl)-phenyl]-benzamide

The title compound 946 was produced in substantially the same manner as in Example L.

¹H-NMR (CDCL₃, 400 MHz): δ 12.17 (1H, d, J=8.8 Hz), 12.23 (1H, d, J=12.4 Hz), 8.70 (1H, dd, J=9.3 Hz, J=20.7 Hz), 8.14-8.27 (3H, m), 7.95-8.01 (1H, m), 7.68-7.74 (2H, m), 7.26-7.46 (3H, m), 6.78-6.82 (2H, m), 3.50-4.20 (9H, m), 2.35-2.63 (6H, m), 1.92-2.05 (2H, m), 1.00-1.30 (6H, m)

Mass spectrometric value (ESI-MS) 600 (M−1)

Compound 947 3-{[Bis-(2-hydroxy-propyl)-amino]-methyl}-N-[2-(4-fluoro-benzylidene-hydrazinocarbonyl)-4-(2-oxo-pyrrolidin-1-yl)-phenyl]-benzamide

The title compound 947 was produced in substantially the same manner as in Example L.

¹H-NMR (CDCL₃, 400 MHz): δ 12.21 (1H, d, J=5.4 Hz), 11.44 (1H, d, J=12.4 Hz), 8.70 (1H, dd, J=9.0 Hz, J=26.1 Hz), 8.20-8.35 (3H, m), 7.96-7.99 (1H, m), 7.72-7.82 (2H, m), 7.38-7.46 (2H, m), 7.25-7.32 (1H, m), 6.93-6.99 (2H, m), 3.50-4.10 (6H, m), 2.35-2.64 (6H, m), 1.87-1.97 (2H, m), 1.07-1.14 (6H, m)

Mass spectrometric value (ESI-MS) 588 (M−1)

Compound 948 3-{[Bis-(2-hydroxy-propyl)-amino]-methyl}-N-[2-(4-methyl-benzylidene-hydrazinocarbonyl)-4-(2-oxo-pyrrolidin-1-yl)-phenyl]-benzamide

The title compound 948 was produced in substantially the same manner as in Example L.

¹H-NMR (CDCL₃, 400 MHz): δ 12.13 (1H, d, J=3.0 Hz), 11.28 (1H, d, J=11.4 Hz), 8.68 (1H, dd, J=9.2 Hz, J=20.5 Hz), 8.16-8.29 (3H, m), 7.94-8.00 (1H, m), 7.60-7.70 (2H, m), 7.25-7.45 (3H, m), 7.06-7.11 (2H, m), 3.52-4.07 (6H, m), 2.20-2.61 (9H, m), 1.90-2.00 (2H, m), 1.09-1.30 (6H, m)

Mass spectrometric value (ESI-MS) 584 (M−1)

Example M Compound 949 3-{[Bis-(2-hydroxy-propyl)-amino]-methyl}-N-[2-(3,4-dimethyl-benzylidene-hydrazinocarbonyl)-4-(2-hydroxy-3-piperidin-1-yl-propoxy)-phenyl]-benzamide

2-Amino-5-hydroxy-benzoic acid methyl ester (compound A) (350 mg) was dissolved in anhydrous methylene chloride (20 ml). Pyridine (230 mg) and 3-(chloromethyl)benzoic acid (compound B) (540 mg) were added dropwise to the solution at 0° C., and the mixture was stirred at room temperature for 10 min. After the completion of the reaction, distilled water was added thereto at room temperature, and the mixture was subjected to separatory extraction with chloroform. The organic layer was washed with saturated brine, was dried over sodium sulfate, and was then concentrated under the reduced pressure. The residue was purified by column chromatography eluted with a chloroform-methanol system to give 2-(3-chloromethyl-benzoylamino)-5-hydroxy-benzoic acid methyl ester as a useful intermediate (280 mg, yield 42%).

Subsequently, 2-(3-chloromethyl-benzoylamino)-5-hydroxy-benzoic acid methyl ester (280 mg) produced by the above reaction was dissolved in anhydrous methylene chloride (20 ml). Triethylamine (180 mg) and diisopropanolamine (compound B′) (230 mg) were added dropwise to the solution at room temperature, and the mixture was stirred at that temperature for 12 hr. After the completion of the reaction, distilled water was added thereto at room temperature, and the mixture was subjected to separatory extraction with chloroform. The organic layer was washed with saturated brine, was dried over sodium sulfate, and was then concentrated under the reduced pressure. The residue was purified by column chromatography eluted with a chloroform-methanol system to give 2-(3-{[bis-(2-hydroxy-propyl)-amino]-methyl}benzoylamino)-5-hydroxy-benzoic acid methyl ester (58 mg, yield 16%).

2-(3-{[Bis-(2-hydroxy-propyl)-amino]-methyl}-benzoylamino)-5-hydroxy-benzoic acid methyl ester (60 mg) produced by the above process was dissolved in N,N-dimethylformamide (5 ml). Potassium carbonate (58 mg) and epibromohydrin (58 mg: dissolved in 2 ml of N,N-dimethylformamide) were added to the solution at room temperature, and the mixture was stirred at that temperature for 12 hr. After the completion of the reaction, distilled water was added thereto at room temperature, and the mixture was subjected to separatory extraction with ethyl acetate. The organic layer was washed with saturated brine, was dried over sodium sulfate, and was then concentrated under the reduced pressure. The residue was purified by column chromatography eluted with a chloroform-methanol system to give 2-(3-{[bis-(2-hydroxy-propyl)-amino]-methyl}-benzoylamino)-5-oxilanylmethoxy-benzoic acid methyl ester as a useful intermediate (68 mg, yield 66%).

2-(3-{[Bis-(2-hydroxy-propyl)-amino]-methyl}-benzoylamino)-5-oxilanylmethoxy-benzoic acid methyl ester (12 mg) produced by the above process was dissolved in anhydrous methylene chloride (5 ml). Piperidine (6.5 mg: dissolved in 1 ml of anhydrous methylene chloride) and a catalytic amount of ytterbium (III) trifluoromethanesulfonate were added to the solution at room temperature, and the mixture was stirred at that temperature for 12 hr. After the completion of the reaction, distilled water was added thereto at room temperature, and the mixture was subjected to separatory extraction with chloroform. The organic layer was washed with saturated brine, was dried over sodium sulfate, and was then concentrated under the reduced pressure. The residue was purified by column chromatography eluted with a chloroform-methanol system to give 2-(3-{[bis-(2-hydroxy-propyl)amino]methyl}benzoylamino)-5-(2-hydroxy-3-piperidin-1-yl-propoxy)-benzoic acid methyl ester (10 mg, yield 71%).

Subsequently, 2-(3-{[bis-(2-hydroxy-propyl)-amino]-methyl}-benzoylamino)-5-(2-hydroxy-3-piperidin-1-yl-propoxy)-benzoic acid methyl ester (13 mg) produced by the above process was dissolved in ethanol (5 ml). Hydrazine monohydrate (1 ml) was added dropwise to the solution at room temperature, and the mixture was stirred at that temperature for 12 hr. After the completion of the reaction, the reaction solution was concentrated under the reduced pressure, and the residue was purified by column chromatography eluted with a chloroform-methanol system to give 3-{[bis-(2-hydroxy-propyl)-amino]-methyl}-N-[2-hydrazinocarbonyl-4-(2-hydroxy-3-piperidin-1-yl-propoxy)-phenyl]-benzamide (5.8 mg, yield 45%).

3-{[Bis-(2-hydroxy-propyl)-amino]-methyl}-N-[2-hydrazinocarbonyl-4-(2-hydroxy-3-piperidin-1-yl-propoxy)-phenyl]-benzamide (5.8 mg) produced by the above process was dissolved in anhydrous toluene (5 ml). 3,4-Dimethylbenzaldehyde (compound C) (3 mg: dissolved in 1 ml of anhydrous toluene) and a catalytic amount of acetic acid were added dropwise to the solution at room temperature, and the mixture was stirred at that temperature for 6 hr. After the completion of the reaction, the reaction solution was neutralized with a saturated aqueous sodium hydrogencarbonate solution, and was then subjected to separatory extraction with ethyl acetate. The organic layer was washed with saturated brine, was dried over sodium sulfate, and was then concentrated under the reduced pressure. The residue was purified by column chromatography eluted with a chloroform-methanol system to give the title compound 949 (4.0 mg, yield 60%).

¹H-NMR (CDCL₃, 400 MHz): δ 11.97 (1H, bs), 7.94-8.65 (4H, m), 6.98-7.65 (7H, m), 3.52-4.45 (7H, m), 1.50-2.90 (16H, m), 1.20-1.30 (6H, m), 1.00-1.18 (6H, m)

Mass spectrometric value (ESI-MS) 672 (M−1)

Compound 950 3-{[Bis-(2-hydroxy-propyl)-amino]-methyl}-N-[2-(4-chloro-3-trifluoromethyl-benzylidene-hydrazinocarbonyl)-4-(2-hydroxy-3-piperidin-1-yl-propoxy)-phenyl]-benzamide

The title compound 950 was produced in substantially the same manner as in Example M.

¹H-NMR (CDCL₃, 400 MHz): δ 12.10-12.20 (1H, m), 7.20-8.70 (10H, m), 6.95-7.05 (1H, m), 1.50-4.25 (17H, m), 1.20-1.30 (6H, m), 0.85-1.18 (6H, m)

Mass spectrometric value (ESI-MS) 746 (M−1)

Compound 951 3-{[Bis-(2-hydroxy-propyl)-amino]-methyl}-N-[4-(3-diethylamino-2-hydroxy-propoxy)-2-(3,4-dimethyl-benzylidene-hydrazinocarbonyl)-phenyl]-benzamide

The title compound 951 was produced in substantially the same manner as in Example M.

¹H-NMR (CDCL₃, 400 MHz): δ 12.02 (1H, bs), 8.58-8.65 (1H, m), 8.47 (1H, s), 8.17-8.24 (1H, m), 7.80-8.00 (1H, m), 7.27-7.60 (5H, m), 6.98-7.10 (2H, m), 1.50-4.12 (23H, m), 1.20-1.28 (6H, m), 1.08-1.16 (6H, m)

Mass spectrometric value (ESI-MS) 660 (M−1)

Compound 952 3-{[Bis-(2-hydroxy-propyl)-amino]-methyl}-N-[2-(4-chloro-3-trifluoromethyl-benzylidene-hydrazinocarbonyl)-4-(3-diethylamino-2-hydroxy-propoxy)-phenyl]-benzamide

The title compound 952 was produced in substantially the same manner as in Example M.

¹H-NMR (CDCL₃, 400 MHz): δ 12.21 (1H, d, J=16.1 Hz), 8.64-8.67 (1H, m), 8.50-8.58 (1H, m), 8.30-8.38 (1H, m), 7.80-8.12 (3H, m), 7.35-7.50 (4H, m), 6.97-7.00 (1H, m), 1.50-4.50 (17H, m), 1.20-1.35 (6H, m), 1.08-1.17 (6H, m)

Mass spectrometric value (ESI-MS) 734 (M−1)

Compound 953 3-{[Bis-(2-hydroxy-propyl)-amino]-methyl}-N-[2-(3,4-dimethyl-benzylidene-hydrazinocarbonyl)-4-(2-hydroxy-3-morpholin-4-yl-propoxy)-phenyl]-benzamide

The title compound 953 was produced in substantially the same manner as in Example M.

Mass spectrometric value (ESI-MS) 674 (M−1)

Compound 954 3-{[Bis-(2-hydroxy-propyl)-amino]-methyl}-N-[2-(4-chloro-3-trifluoromethyl-benzylidene-hydrazinocarbonyl)-4-(2-hydroxy-3-morpholin-4-yl-propoxy)-phenyl]-benzamide

The title compound 954 was produced in substantially the same manner as in Example M.

Mass spectrometric value (ESI-MS) 748 (M−1)

Example N Compound 955 N-[3-(4-Chloro-3-trifluoromethyl-benzylidene-hydrazinocarbonyl)-5-methyl-thiophen-2-yl]-3,4-dimethoxy-benzamide

Methyl 2-aminothiophene-3-carboxylate (compound A) (160 mg) was dissolved in anhydrous methylene chloride (5 ml). Pyridine (120 mg: dissolved in 2 ml of anhydrous methylene chloride) and 3,4-dimethoxybenzoyl chloride (compound B) (300 mg) were added to the solution at 0° C., and the mixture was stirred at room temperature for 12 hr. After the completion of the reaction, distilled water was added thereto at room temperature, and the mixture was subjected to separatory extraction with chloroform. The organic layer was washed with saturated brine, was dried over sodium sulfate, and was then concentrated under the reduced pressure. The residue was purified by column chromatography using a hexane-acetone system to give 2-(3,4-dimethoxy-benzoylamino)-thiophene-3-carboxylic acid methyl ester (320 mg, yield 100%).

Separately, phosphorus oxychloride (100 μl) was added dropwise to N,N-dimethylformamide (29 mg) at 0° C., and the mixture was stirred at that temperature for 5 min. Subsequently, the reaction system was heated to 80° C., 2-(3,4-dimethoxy-benzoylamino)-thiophene-3-carboxylic acid methyl ester (64 mg: dissolved in 1 ml of N,N-dimethylformamide) produced by the above reaction was then added dropwise thereto, and the mixture was stirred at that temperature for 2 hr. After the completion of the reaction, the reaction solution was neutralized with a saturated sodium hydrogencarbonate solution, and was then subjected to separatory extraction with chloroform. The organic layer was washed with saturated brine, was dried over sodium sulfate, and was then concentrated under the reduced pressure to give crude 2-(3,4-dimethoxy-benzoylamino)-5-formylthiophene-3-carboxylic acid methyl ester (70 mg, crude yield 100%).

Crude 2-(3,4-dimethoxy-benzoylamino)-5-formylthiophene-3-carboxylic acid methyl ester (35 mg) synthesized by the above process was dissolved in tetrahydrofuran/N,N-dimethylformamide=1/1 (10 ml). Sodium borohydride (22 mg) was added to the solution at room temperature, and the mixture was stirred at that temperature for 20 min. After the completion of the reaction, distilled water was added thereto at room temperature, and the mixture was subjected to separatory extraction with chloroform. The organic layer was washed with saturated brine, was dried over sodium sulfate, and was then concentrated under the reduced pressure to give crude 2-(3,4-dimethoxy-benzoylamino)-5-hydroxymethyl-thiophene-3-carboxylic acid methyl ester (35 mg, crude yield 100%).

Subsequently, crude 2-(3,4-dimethoxy-benzoylamino)-5-hydroxy-methyl-thiophene-3-carboxylic acid methyl ester (crude 35 mg) synthesized by the above process was dissolved in anhydrous methylene chloride (5 ml). Pyridine (24 mg: dissolved in 1 ml of anhydrous methylene chloride) and acetic anhydride (31 mg: dissolved in 1 ml of anhydrous methylene chloride) were added dropwise to the solution at room temperature, and the mixture was stirred at that temperature for 12 hr. After the completion of the reaction, distilled water was added thereto at room temperature, and the mixture was subjected to separatory extraction with chloroform. The organic layer was washed with saturated brine, was dried over sodium sulfate, and was then concentrated under the reduced pressure. The residue was purified by column chromatography eluted with a chloroform-methanol system to give 5-acetoxymethyl-2-(3,4-dimethoxy-benzoylamino)-thiophene-3-carboxylic acid methyl ester as a useful intermediate (26 mg, 3 steps, yield 67%).

5-Acetoxymethyl-2-(3,4-dimethoxy-benzoylamino)-thiophene-3-carboxylic acid methyl ester (26 mg) produced by the above process was dissolved in ethanol/tetrahydrofuran=5/2 (7 ml), and 10% palladium-carbon (10 mg) was added to the solution at room temperature. The air in the reaction system was replaced by hydrogen, and the mixture was then stirred at that temperature for 12 hr. After the completion of the reaction, the atmosphere in the reaction system was replaced by nitrogen, and the reaction solution was then filtered through Celite to remove 10% palladium-carbon and was then concentrated under the reduced pressure. The residue was purified by column chromatography using a hexane-acetone system to give 2-(3,4-dimethoxy-benzoylamino)-5-methyl-thiophene-3-carboxylic acid methyl ester (13 mg, yield 59%).

Subsequently, 2-(3,4-dimethoxy-benzoylamino)-5-methyl-thiophene-3-carboxylic acid methyl ester (16 mg) synthesized by the above process was dissolved in ethanol (5 ml). Hydrazine (1 ml) was then added to the solution at room temperature, and the mixture was stirred at that temperature for 12 hr. After the completion of the reaction, the reaction system was concentrated under the reduced pressure, and the residue was purified by column chromatography eluted with a chloroform-methanol system to give N-(3-hydrazinocarbonyl)-5-methylthiophen-2-yl)-3,4-dimethoxy-benzamide (8.0 mg, yield 50%).

Subsequently, N-(3-hydrazinocarbonyl)-5-methylthiophen-2-yl)-3,4-dimethoxy-benzamide (8.0 mg) was dissolved in anhydrous toluene (5 ml), 4-chloro-3-(trifluoromethyl)benzaldehyde (compound C) (15 mg: dissolved in 1 ml of anhydrous toluene) and a catalytic amount of acetic acid were added dropwise to the solution at room temperature, and the mixture was stirred at that temperature for 3 hr. After the completion of the reaction, the reaction solution was neutralized with a saturated sodium hydrogencarbonate solution and was then subjected to separatory extraction with ethyl acetate. The organic layer was washed with saturated brine, was dried over sodium sulfate, and was then concentrated under the reduced pressure. The residue was purified by column chromatography eluted with a chloroform-methanol system to give the title compound 955 (5.0 mg, yield 38%).

¹H-NMR (CDCL₃, 400 MHz): δ 12.66 (1H, bs), 9.19 (1H, bs), 8.19 (1H, bs), 8.02 (1H, s), 7.80-7.92 (1H, m), 7.62-7.65 (2H, m), 7.56 (1H, d, J=8.3 Hz), 6.92 (1H, d, J=8.8 Hz), 3.97 (3H, s), 3.95 (3H, s), 2.44 (3H, s)

Mass spectrometric value (ESI-MS) 524 (M−1)

Example O Compound 956 N-[3-(4-Chloro-3-trifluoromethyl-benzylidene-hydrazinocarbonyl)-4-methyl-5-piperidin-1-ylmethyl-thiophen-2-yl]-3-diethylaminomethyl-benzamide

Ethyl-2-amino-4-methylthiophene-3-carboxylate (compound A) (370 mg) was dissolved in anhydrous methylene chloride (10 ml). Pyridine (240 mg: dissolved in 2 ml of anhydrous methylene chloride) and 3-(chloromethyl)benzoyl chloride (compound B) (570 mg: dissolved in 2 ml of anhydrous methylene chloride) were added dropwise to the solution at 0° C., and the mixture was stirred at room temperature for 12 hr. After the completion of the reaction, distilled water was added thereto at room temperature, and the mixture was then subjected to separatory extraction with chloroform. The organic layer was washed with saturated brine, was dried over sodium sulfate, and was then concentrated under the reduced pressure. The residue was purified by column chromatography eluted with a chloroform-methanol system to give 2-(3-chloromethylbenzoylamino)-4-methyl-thiophene-3-carboxylic acid ethyl ester (670 mg, yield 99%).

Subsequently, 2-(3-diethylaminomethyl-benzoylamino)-4-methyl-thiophene-3-carboxylic acid ethyl ester (700 mg) synthesized by the above process was dissolved in anhydrous methylene chloride (10 ml). Triethylamine (425 mg: dissolved in 2 ml of anhydrous methylene chloride) and diethylamine (compound B′) (310 mg: dissolved in 2 ml of anhydrous methylene chloride) were added dropwise to the solution at 0° C., and the mixture was stirred at room temperature for 2 hr. After the completion of the reaction, distilled water was added thereto at room temperature, and the mixture was then subjected to separatory extraction with chloroform, and the organic layer was washed with saturated brine, was dried over sodium sulfate, and was then concentrated under the reduced pressure. The residue was purified by column chromatography eluted with a chloroform-methanol system to give 2-(3-diethylaminomethyl-benzoylamino)-4-methylthiophene-3-carboxylic acid ethyl ester (690 mg, yield 88%).

Separately, phosphorus oxychloride (200 μl) was added dropwise to N,N-dimethylformamide (73 mg) at 0° C., and the mixture was stirred at that temperature for 5 min. The reaction system was heated to 80° C., 2-(3-diethylaminomethyl-benzoylamino)-4-methyl-thiophene-3-carboxylic acid ethyl ester (187 mg) synthesized by the above process was then added thereto, and the mixture was stirred at that temperature for 3 hr. After the completion of the reaction, the reaction solution was neutralized with a saturated sodium hydrogencarbonate solution, and was then subjected to separatory extraction with chloroform, and the organic layer was washed with saturated brine, was dried over sodium sulfate, and was then concentrated under the reduced pressure. The residue was purified by column chromatography eluted with a chloroform-methanol system to give 2-(3-diethylaminomethyl-benzoylamino)-5-formyl-4-methylthiophene-3-carboxylic acid ethyl ester as a useful intermediate (110 mg, yield 53%).

2-(3-diethylaminomethyl-benzoylamino)-5-formyl-4-methyl-thiophene-3-carboxylic acid ethyl ester (110 mg) synthesized by the above process was dissolved in N,N-dimethylformamide (10 ml), acetic acid (100 μl) and sodium triacetoxyborohydride (66 mg) were added to the solution at room temperature, and the mixture was stirred at that temperature for one hr. After the completion of the reaction, the reaction solution was neutralized with a saturated sodium hydrogencarbonate solution, and was then subjected to separatory extraction with ethyl acetate. The organic layer was washed with saturated brine, was dried over sodium sulfate, and was then concentrated under the reduced pressure. The residue was purified by column chromatography eluted with a chloroform-methanol system to give 2-(3-diethylaminomethyl-benzoylamino)-4-methyl-5-piperidin-1-ylmethylthiophene-3-carboxylic acid ethyl ester (79 mg, yield 64%).

Subsequently, 2-(3-diethylaminomethyl-benzoylamino)-4-methyl-5-piperidin-1-ylmethylthiophene-3-carboxylic acid ethyl ester (79 mg) was dissolved in ethanol (10 ml), hydrazine monohydrate (2 ml) was added dropwise to the solution at room temperature, and a reaction was then allowed to proceed at that temperature for 12 hr. After the completion of the reaction, the reaction system was concentrated under the reduced pressure. The residue was purified by column chromatography eluted with a chloroform-methanol system to give 3-diethylaminomethyl-N-(3-hydrazinocarbonyl-4-methyl-5-piperidin-1-ylmethylthiophen-2-yl)-benzamide as a useful intermediate (30 mg, yield 38%).

Subsequently, 3-diethylaminomethyl-N-(3-hydrazinocarbonyl-4-methyl-5-piperidin-1-ylmethylthiophen-2-yl)-benzamide (15 mg) produced by the above process was dissolved in anhydrous toluene. 4-Chloro-3-(trifluoromethyl)benzaldehyde (compound C) (21 mg: dissolved in 1 ml of anhydrous toluene) and a catalytic amount of acetic acid were added dropwise to the solution at room temperature, and the mixture was then stirred at that temperature for 3 hr. After the completion of the reaction, the reaction solution was neutralized with a saturated sodium hydrogencarbonate solution, and was then subjected to separatory extraction with ethyl acetate, and the organic layer was washed with saturated brine, was dried over sodium sulfate, and was then concentrated under the reduced pressure. The residue was purified by column chromatography eluted with a chloroform-methanol system to give the title compound 956 (6.0 mg, yield 29%).

¹H-NMR (CDCL₃, 400 MHz): δ 8.26 (1H, bs), 8.05 (1H, s), 8.00 (1H, s), 7.95 (1H, d, J=8.0 Hz), 7.88 (1H, d, J=7.6 Hz), 7.55-7.62 (2H, m), 7.42-7.48 (1H, m), 3.67 (2H, s), 2.48-2.60 (10H, m), 1.24-2.00 (9H, m), 1.07 (6H, t, J=7.1 Hz)

Mass spectrometric value (ESI-MS) 646 (M−1)

Compound 957 3-Diethylaminomethyl-N-[3-(4-methoxy-benzylidene-hydrazinocarbonyl)-4-methyl-5-piperidin-1-ylmethyl-thiophen-2-yl]-benzamide

The title compound 957 was produced in substantially the same manner as in Example O.

¹H-NMR (CDCL₃, 400 MHz): δ 8.08 (1H, bs), 7.99 (1H, bs), 7.90 (1H, d, J=7.8 Hz), 7.74 (2H, d, J=8.3 Hz), 7.60 (1H, d, J=7.6 Hz), 7.40-7.45 (1H, m), 6.94 (2H, d, J=8.8 Hz), 3.86 (3H, s), 3.67 (2H, s), 2.40-2.60 (10H, m), 1.25-1.62 (9H, m), 1.06 (6H, t, J=7.1 Hz)

Mass spectrometric value (ESI-MS) 574 (M−1) 598 (M+23)

Compound 958 3-{[Bis-(2-hydroxy-propyl)-amino]-methyl}-N-[2-(4-methoxy-benzylidene-hydrazinocarbonyl)-4-piperidin-1-yl-phenyl]-benzamide

The title compound 958 was produced in substantially the same manner as in Example J.

¹H-NMR (CD₃OD, 400 MHz): δ 8.38 (1H, dd, J=6.1 Hz, J=9.0 Hz), 8.29 (1H, s), 8.01 (1H, bs), 7.86 (1H, d, J=7.4 Hz), 7.75-7.85 (2H, m), 7.59 (1H, d, J=7.3 Hz), 7.48 (1H, dd, J=7.6 Hz, J=7.8 Hz), 7.37 (1H, d, J=2.7 Hz), 7.22 (1H, dd, J=3.0 Hz, J=9.0 Hz), 6.90-7.03 (2H, m), 3.80-3.90 (7H, m), 3.22-3.30 (4H, m), 2.40-2.60 (4H, m), 1.70-1.89 (4H, m), 1.62-1.64 (2H, m), 1.08 (3H, d, J=6.3 Hz), 1.07 (3H, d, J=6.1 Hz)

Mass spectrometric value (ESI-MS) 600, 601 (M−1) 622 (M−1+23)

Example P Compound 959 3-{[Bis-(2-hydroxy-propyl)-amino]-methyl}-N-[3-(3-fluoro-benzylidene-hydrazinocarbonyl)-naphthalen-2-yl]-benzamide

3-Amino-naphthalene-2-carboxylic acid (compound A′) (1.2 g) was dissolved in anhydrous methylene chloride (12 ml). 1-(3-Dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (2.5 g), 1-hydroxybenzotriazole monohydrate (1.5 g), and triethylamine (1 ml) were added to the solution at room temperature, and the mixture was then stirred at that temperature for 12 hr. After the completion of the reaction, distilled water was added thereto at room temperature, and the mixture was subjected to separatory extraction with chloroform. The organic layer was washed with saturated brine, was dried over sodium sulfate, and was then concentrated under the reduced pressure. The residue was purified by column chromatography using a hexane-acetone system to give 3-amino-naphthalene-2-carboxylic acid methyl ester as a useful intermediate (compound A) (530 mg, yield 41%).

3-Amino-naphthalene-2-carboxylic acid methyl ester (compound A) (530 mg) produced by the above process was dissolved in anhydrous methylene chloride (10 ml). Pyridine (0.5 ml) and 3-(chloromethyl)benzoyl chloride (compound B) (0.6 ml) was added dropwise to the solution at room temperature, and the mixture was then stirred at that temperature for 30 min. After the completion of the reaction, distilled water was added thereto at room temperature, and the mixture was subjected to separatory extraction with chloroform. The organic layer was washed with saturated brine, was dried over sodium sulfate, and was concentrated under the reduced pressure to precipitate crystals. The crystals were collected by Kiriyama Rohto and were washed with a hexane-ether solvent to give 3-(3-chloromethylbenzoylamino)-naphthalene-2-carboxylic acid methyl ester (870 mg, yield 93%).

Subsequently, 3-(3-chloromethyl-benzoylamino)-naphthalene-2-carboxylic acid methyl ester (870 mg) was dissolved in anhydrous methylene chloride (15 ml). Pyridine (400 μl) and diisopropanolamine (compound B′) (1.0 g) were added to the solution at room temperature, and the mixture was then stirred at that temperature for 48 hr. After the completion of the reaction, distilled water was added thereto at room temperature, and the mixture was subjected to separatory extraction with chloroform. The organic layer was washed with saturated brine, was dried over sodium sulfate, and was then concentrated under the reduced pressure. The residue was purified by column chromatography eluted with a hexane-acetone system to give 3-(3-{[bis-(2-hydroxy-propyl)-amino]-methyl}-benzoylamino)-naphthalene-2-carboxylic acid methyl ester as a useful intermediate (640 mg).

3-(3-{[Bis-(2-hydroxy-propyl)-amino]-methyl}-benzoylamino)-naphthalene-2-carboxylic acid methyl ester (640 mg) produced by the above reaction was dissolved in ethanol (7 ml). Hydrazine monohydrate (1 ml) was added dropwise to the solution at room temperature, and the mixture was then stirred at that temperature for 2 hr. After the completion of the reaction, the reaction solution was concentrated under the reduced pressure, and the residue was purified by column chromatography eluted with a chloroform-methanol system to give 3-{[bis-(2-hydroxy-propyl)amino]-methyl}-N-(3-hydrazinocarbonylnaphthalen-2-yl)-benzamide (350 mg, yield 54%).

Subsequently, 3-{[bis-(2-hydroxy-propyl)amino]-methyl}-N-(3-hydrazinocarbonylnaphthalen-2-yl)-benzamide (50 mg) was dissolved in anhydrous toluene (1 ml). 3-Fluorobenzaldehyde (compound C) (50 μl) was added dropwise to the solution at room temperature, and the mixture was then stirred at 120° C. for 12 hr. After the completion of the reaction, the reaction solution was allowed to stand for cooling at room temperature and the reaction system was then concentrated under the reduced pressure. The residue was purified by column chromatography eluted with a hexane-acetone system to give the title compound 959 (32 mg, yield 51%).

¹H-NMR (CDCL₃, 400 MHz): δ 12.05 (1H, bs), 11.40-11.55 (1H, m), 8.86 (1H, d, J=18.6 Hz), 8.10-8.40 (3H, m), 7.88 (1H, dd, J=7.3 Hz, J=17.8 Hz), 7.66 (2H, d, J=8.3 Hz), 7.25-7.50 (5H, m), 7.05-7.15 (2H, m), 6.80-6.95 (1H, m), 4.15-4.25 (2H, m), 3.95-4.05 (2H, m), 3.89 (1H, s), 3.60 (1H, d, J=1.4 Hz), 2.48-2.83 (4H, m), 1.20 (3H, d, J=6.1 Hz), 1.14 (3H, d, J=6.3 Hz)

Mass spectrometric value (ESI-MS) 555 (M−1)

Compound 960 3-{[Bis-(2-hydroxy-propyl)-amino]-methyl}-N-[3-(4-methyl-benzylidene-hydrazinocarbonyl)-naphthalen-2-yl]-benzamide

The title compound 960 was produced in substantially the same manner as in Example P.

¹H-NMR (CDCL₃, 400 MHz): δ 11.90 (1H, bs), 10.90-11.00 (1H, m), 8.85 (1H, bs), 8.30 (1H, d, J=3.9 Hz), 7.86-8.20 (3H, m), 7.52-7.64 (3H, m), 7.28-7.46 (4H, m), 7.06-7.18 (1H, m), 6.88 (2H, d, J=7.8 Hz), 3.80-3.96 (4H, m), 3.55-3.60 (1H, m), 2.40-2.70 (4H, m), 2.18-2.23 (3H, m), 1.10 (3H, d, J=6.1 Hz), 1.06 (3H, d, J=6.1 Hz)

Mass spectrometric value (ESI-MS) 551 (M−1)

Compound 961 3-{[Bis-(2-hydroxy-propyl)-amino]-methyl}-N-[3-(3,4-dimethyl-benzylidene-hydrazinocarbonyl)-naphthalen-2-yl]-benzamide

The title compound 961 was produced in substantially the same manner as in Example P.

¹H-NMR (CDCL₃, 400 MHz): δ 11.95-12.05 (1H, m), 10.80-10.95 (1H, m), 8.95-9.02 (1H, m), 8.15-8.32 (3H, m), 7.95-8.05 (1H, m), 7.20-7.80 (8H, m), 6.87 (1H, d, J=7.3 Hz), 3.60-4.20 (4H, m), 2.28-2.75 (4H, m), 2.00-2.15 (6H, m), 1.10-1.17 (6H, m)

Mass spectrometric value (ESI-MS) 565 (M−1)

Compound 962 3-{[Bis-(2-hydroxy-propyl)-amino]-methyl}-N-[3-(4-chloro-3-trifluoromethyl-benzylidene-hydrazinocarbonyl)-naphthalen-2-yl]-benzamide

The title compound 962 was produced in substantially the same manner as in Example P.

¹H-NMR (CDCL₃, 400 MHz): δ 11.96-12.05 (1H, m), 11.71 (1H, d, J=15.1 Hz), 8.80 (1H, s), 8.32 (2H, bs), 8.13 (1H, d, J=7.8 Hz), 7.57-7.94 (4H, m), 7.25-7.46 (5H, m), 7.08 (2H, d, J=8.0 Hz), 3.50-4.20 (5H, m), 2.30-2.86 (4H, m), 1.13 (3H, d, J=6.1 Hz), 1.09 (3H, d, J=6.3 Hz)

Mass spectrometric value (ESI-MS) 639, 641, 642 (M−1)

Compound 963 3-{[Bis-(2-hydroxy-propyl)-amino]-methyl}-N-[3-(4-methoxy-benzylidene-hydrazinocarbonyl)-naphthalen-2-yl]-benzamide

The title compound 963 was produced in substantially the same manner as in Example P.

¹H-NMR (CDCL₃, 400 MHz): δ 11.95 (1H, bs), 10.86-11.00 (1H, m), 8.80-8.90 (1H, m), 8.05-8.30 (3H, m), 7.85-7.95 (1H, m), 7.60-7.65 (3H, m), 7.22-7.48 (4H, m), 7.06-7.18 (1H, m), 6.59 (1H, d, J=8.5 Hz), 3.50-3.96 (8H, m), 2.40-2.70 (4H, m), 1.10 (3H, d, J=6.1 Hz), 1.06 (3H, d, J=6.1 Hz)

Mass spectrometric value (ESI-MS) 567 (M−1) 591 (M+23)

Compound 964 3-{[Bis-(2-hydroxy-propyl)-amino]-methyl}-N-[3-(3-fluoro-benzylidene-hydrazinocarbonyl)-pyridin-2-yl]-benzamide

The title compound 964 was produced in substantially the same manner as in Example P.

¹H-NMR (CD₃OD, 400 MHz): δ 8.55-8.60 (1H, m), 8.29 (1H, s), 8.25 (1H, d, J=7.8 Hz), 8.07 (1H, s), 7.89-7.96 (1H, m), 7.70 (1H, d, J=10.0 Hz), 7.62 (1H, d, J=7.6 Hz), 7.57 (1H, d, J=7.3 Hz), 7.40-7.52 (2H, m), 7.32-7.40 (1H, m), 7.13-7.20 (1H, m), 3.60-3.95 (4H, m), 2.35-2.60 (4H, m), 1.08 (3H, d, J=6.1 Hz), 1.07 (3H, d, J=6.3 Hz)

Mass spectrometric value (ESI-MS) 506, 507, 508 (M−1)

Compound 965 3-{[Bis-(2-hydroxy-propyl)-amino]-methyl}-N-[3-(4-methyl-benzylidene-hydrazinocarbonyl)-pyridin-2-yl]-benzamide

The title compound 965 was produced in substantially the same manner as in Example P.

¹H-NMR (CD₃OD, 400 MHz): δ 8.54-8.59 (1H, m), 8.21-8.28 (2H, m), 8.05-8.09 (1H, m), 7.86-7.95 (1H, m), 7.72 (2H, d, J=7.8 Hz), 7.62 (1H, d, J=7.8 Hz), 7.49 (1H, ddd, J=1.7 Hz, J=7.6 Hz, J=7.6 Hz), 7.32-7.37 (1H, m), 7.25 (2H, d, J=7.8 Hz), 3.81-3.93 (4H, m), 2.39-2.60 (4H, m), 2.37 (3H, s), 1.08 (3H, d, J=6.1 Hz), 1.07 (3H, d, J=6.4 Hz)

Mass spectrometric value (ESI-MS) 502, 503, 504 (M−1) 526, 527 (M+23)

Compound 966 3-{[Bis-(2-Hydroxy-Propyl)-Amino]-Methyl}-N-[3-(3,4-dimethyl-benzylidene-hydrazinocarbonyl)-pyridin-2-yl]-benzamide

The title compound 966 was produced in substantially the same manner as in Example P.

¹H-NMR (CD₃OD, 400 MHz): δ 8.50-8.60 (1H, m), 8.23-8.28 (2H, m), 8.05-8.08 (1H, m), 7.88-7.98 (1H, m), 7.60-7.66 (2H, m), 7.46-7.56 (2H, m), 7.25-7.40 (1H, m), 7.18-7.22 (1H, m), 3.75-3.94 (4H, m), 2.38-2.60 (4H, m), 2.31 (3H, s), 2.30 (3H, s), 1.08 (3H, d, J=6.1 Hz), 1.07 (3H, d, J=6.1 Hz)

Mass spectrometric value (ESI-MS) 516, 517 (M−1) 540, 541 (M+23)

Compound 967 3-{[Bis-(2-hydroxy-propyl)-amino]-methyl}-N-[3-(4-chloro-3-trifluoromethyl-benzylidene-hydrazinocarbonyl)-pyridin-2-yl]-benzamide

The title compound 967 was produced in substantially the same manner as in Example P.

¹H-NMR (CDCL₃, 400 MHz): δ 11.70-11.85 (1H, m), 11.61 (1H, s), 8.58 (1H, s), 8.36 (1H, s), 8.24 (1H, s), 8.00-8.10 (2H, m), 7.80-7.90 (1H, m), 7.40-7.55 (4H, m), 6.75-6.85 (1H, m), 3.86-4.10 (4H, m), 2.45-2.75 (4H, m), 1.10 (6H, d, J=6.1 Hz)

Mass spectrometric value (ESI-MS) 592 (M−1) 614 (M+23)

Compound 968 3-{[Bis-(2-hydroxy-propyl)-amino]-methyl}-N-[3-(4-methoxy-benzylidene-hydrazinocarbonyl)-pyridin-2-yl]-benzamide

The title compound 968 was produced in substantially the same manner as in Example P.

¹H-NMR (CDCL₃, 400 MHz): δ 11.74 (1H, s), 11.00-11.20 (1H, m), 8.40-8.45 (1H, m), 8.22 (1H, d, J=12.4 Hz), 8.06 (1H, s), 7.80-7.90 (3H, m), 7.35-7.50 (3H, m), 6.80-7.00 (3H, m), 3.80-3.90 (7H, m), 2.40-2.75 (4H, m), 1.05-1.14 (6H, m)

Mass spectrometric value (ESI-MS) 518 (M−1) 542 (M+23)

Compound 969 N-[3-(3-Fluoro-benzylidene-hydrazinocarbonyl)-naphthalen-2-yl]-3-[4-(2-hydroxy-ethyl)-piperazin-1-ylmethyl]-benzamide

The title compound 969 was produced in substantially the same manner as in Example P.

¹H-NMR (CDCL₃, 400 MHz): δ 11.15 (1H, s), 10.91 (1H, bs), 7.10-8.90 (15H, m), 3.60-3.75 (4H, m), 2.00-2.85 (11H, m)

Mass spectrometric value (ESI-MS) 552, 553 (M−1)

Compound 970 3-[4-(2-Hydroxy-ethyl)-piperazin-1-ylmethyl]-N-[3-(4-methyl-benzylidene-hydrazinocarbonyl)-naphthalen-2-yl]-benzamide

The title compound 970 was produced in substantially the same manner as in Example P.

¹H-NMR (CDCL₃, 400 MHz): δ 11.19 (1H, s), 7.00-8.95 (15H, m), 3.63 (2H, s), 3.59 (2H, t, J=5.4 Hz), 2.50-2.65 (10H, m), 2.40 (3H, s)

Mass spectrometric value (ESI-MS) 548, 549, 550 (M−1)

Compound 971 N-[3-(3,4-Dimethyl-benzylidene-hydrazinocarbonyl)-naphthalen-2-yl]-3-[4-(2-hydroxy-ethyl)-piperazin-1-ylmethyl]-benzamide

The title compound 971 was produced in substantially the same manner as in Example P.

¹H-NMR (CDCL₃, 400 MHz): δ 11.19 (1H, s), 7.00-9.00 (14H, m), 3.63 (2H, s), 3.59 (2H, t, J=5.4 Hz), 2.50-2.75 (10H, m), 2.32 (3H, s), 2.30 (3H, s)

Mass spectrometric value (ESI-MS) 562, 563 (M−1)

Compound 972 N-[3-(4-Chloro-3-trifluoromethyl-benzylidene-hydrazinocarbonyl)-naphthalen-2-yl]-3-[4-(2-hydroxy-ethyl)-piperazin-1-ylmethyl]-benzamide

The title compound 972 was produced in substantially the same manner as in Example P.

¹H-NMR (CDCL₃, 400 MHz): δ 11.19 (1H, s), 8.97 (1H, s), 7.20-8.60 (13H, m), 3.64 (2H, s), 3.57-3.63 (2H, m), 2.50-2.60 (10H, m)

Mass spectrometric value (ESI-MS) 636, 637 (M−1)

Compound 973 3-[4-(2-Hydroxy-ethyl)-piperazin-1-ylmethyl]-N-[3-(4-methoxy-benzylidene-hydrazinocarbonyl)-naphthalen-2-yl]-benzamide

The title compound 973 was produced in substantially the same manner as in Example P.

¹H-NMR (CDCL₃, 400 MHz): δ 11.25 (1H, s), 10.47 (1H, s), 8.88 (1H, s), 8.48 (1H, s), 7.97 (2H, bs), 7.82 (2H, d, J=8.3 Hz), 7.74 (1H, d, J=7.3 Hz), 7.63 (1H, d, J=8.5 Hz), 7.53 (1H, d, J=7.6 Hz), 7.38-7.43 (3H, m), 7.10-7.20 (1H, m), 6.96 (2H, d, J=8.3 Hz), 3.86 (3H, s), 3.62 (2H, s), 3.59 (2H, t, J=5.4 Hz), 2.50-2.60 (10H, m)

Mass spectrometric value (ESI-MS) 564, 565 (M−1)

Compound 974 3-{[Bis-(2-hydroxy-propyl)-amino]-methyl}-N-[4-(3-fluoro-benzylidene-hydrazinocarbonyl)-thiophen-3-yl]-benzamide

The title compound 974 was produced in substantially the same manner as in Example 8.

¹H-NMR (CDCL₃, 400 MHz): δ 8.91 (1H, s), 7.95-8.27 (5H, m), 7.00-7.70 (6H, m), 3.82-4.08 (4H, m), 2.40-2.75 (4H, m), 1.10-1.17 (6H, m)

Mass spectrometric value (ESI-MS) 511, 512 (M−1) 534 (M+23)

Compound 975 3-{[Bis-(2-hydroxy-propyl)-amino]-methyl}-N-[4-(3-methyl-benzylidene-hydrazinocarbonyl)-thiophen-3-yl]-benzamide

The title compound 975 was produced in substantially the same manner as in Example 8.

¹H-NMR (CDCL₃, 400 MHz): δ 11.99 (1H, s), 11.28-11.38 (1H, m), 8.36 (1H, s), 7.95-8.20 (4H, m), 7.68-7.73 (1H, m), 7.35-7.45 (1H, m), 7.15-7.34 (2H, m), 6.87-6.97 (2H, m), 4.10-4.20 (1H, m), 3.85-4.00 (3H, m), 3.65-3.75 (1H, m), 2.62-2.85 (1H, m), 2.30-2.58 (4H, m), 2.15 (3H, s), 1.14 (3H, d, J=6.1 Hz), 1.08 (3H, d, J=6.3 Hz)

Mass spectrometric value (ESI-MS) 507, 508 (M−1) 531 (M+23)

Compound 976 3-{[Bis-(2-hydroxy-propyl)-amino]-methyl}-N-[4-(4-methyl-benzylidene-hydrazinocarbonyl)-thiophen-3-yl]-benzamide

The title compound 976 was produced in substantially the same manner as in Example 8.

¹H-NMR (CDCL₃, 400 MHz): δ 8.99 (1H, s), 7.95-8.30 (4H, m), 7.30-7.70 (4H, m), 7.26 (1H, d, J=6.1 Hz), 7.13 (2H, d, J=7.1 Hz), 3.38-4.05 (4H, m), 2.34-2.70 (7H, m), 1.08-1.15 (6H, m)

Mass spectrometric value (ESI-MS) 507, 508 (M−1) 531 (M+23)

Compound 977 3-{[Bis-(2-hydroxy-propyl)-amino]-methyl}-N-[4-(3,4-dimethyl-benzylidene-hydrazinocarbonyl)-thiophen-3-yl]-benzamide

The title compound 977 was produced in substantially the same manner as in Example 8.

¹H-NMR (CDCL₃, 400 MHz): δ 11.98 (1H, s), 11.12-11.25 (1H, m), 8.30-8.40 (1H, m), 7.96-8.18 (4H, m), 7.70-7.80 (1H, m), 7.20-7.50 (3H, m), 6.75-6.85 (1H, m), 3.65-4.20 (4H, m), 2.45-2.55 (2H, m), 2.20-2.30 (3H, m), 2.10-2.14 (3H, m), 2.02-2.08 (3H, m), 1.14 (3H, d, J=6.1 Hz), 1.08 (3H, d, J=6.3 Hz)

Mass spectrometric value (ESI-MS) 521, 522 (M−1) 545 (M+23)

Compound 978 3-{[Bis-(2-hydroxy-propyl)-amino]-methyl}-N-[4-(4-chloro-3-trifluoromethyl-benzylidene-hydrazinocarbonyl)-thiophen-3-yl]-benzamide

The title compound 978 was produced in substantially the same manner as in Example 8.

¹H-NMR (CDCL₃, 400 MHz): δ 11.85 (1H, d, J=5.1 Hz), 11.65-11.80 (1H, m), 8.28-8.35 (1H, m), 7.98-8.20 (3H, m), 7.65-7.85 (2H, m), 7.02-7.52 (4H, m), 3.60-4.20 (4H, m), 2.46-2.90 (4H, m), 1.14 (3H, d, J=6.1 Hz), 1.09 (3H, d, J=6.1 Hz)

Mass spectrometric value (ESI-MS) 595, 597 (M−1) 619, 621 (M+23)

Compound 979 3-{[Bis-(2-hydroxy-propyl)-amino]-methyl}-N-[4-(4-methoxy-benzylidene-hydrazinocarbonyl)-thiophen-3-yl]-benzamide

The title compound 979 was produced in substantially the same manner as in Example 8.

¹H-NMR (CDCL₃, 400 MHz): δ 12.03 (1H, d, J=10.5 Hz), 11.16-11.30 (1H, m), 8.30-8.40 (1H, m), 7.95-8.15 (3H, m), 7.75 (1H, dd, J=3.2 Hz, J=7.6 Hz), 7.36-7.44 (3H, m), 7.28-7.32 (1H, m), 6.45-6.57 (2H, m), 3.65-4.20 (7H, m), 2.44-2.84 (4H, m), 1.13 (3H, d, J=6.1 Hz), 1.07 (3H, d, J=6.4 Hz)

Mass spectrometric value (ESI-MS) 523, 524 (M−1) 547 (M+23)

Compound 980 N-[4-(3-Fluoro-benzylidene-hydrazinocarbonyl)-thiophen-3-yl]-3-[4-(2-hydroxy-ethyl)-piperazin-1-ylmethyl]-benzamide

The title compound 980 was produced in substantially the same manner as in Example 8.

¹H-NMR (CDCL₃, 400 MHz): δ 8.26 (1H, s), 7.97 (1H, s), 7.87 (1H, d, J=7.8 Hz), 7.00-7.54 (8H, m), 3.59-3.66 (4H, m), 2.50-2.75 (10H, m)

Mass spectrometric value (ESI-MS) 508, 509 (M−1) 532 (M+23)

Compound 981 3-[4-(2-Hydroxy-ethyl)-piperazin-1-ylmethyl]-N-[4-(4-methyl-benzylidene-hydrazinocarbonyl)-thiophen-3-yl]-benzamide

The title compound 981 was produced in substantially the same manner as in Example 8.

¹H-NMR (CDCL₃, 400 MHz): δ 11.81 (1H, bs), 11.50 (1H, bs), 8.24 (1H, s), 7.95 (1H, s), 7.87 (2H, d, J=7.6 Hz), 7.37-7.70 (5H, m), 7.18-7.25 (2H, m), 3.58 (4H, s), 2.37 (3H, s), 2.40-2.55 (10H, m)

Mass spectrometric value (ESI-MS) 504, 505 (M−1) 528 (M+23)

Compound 982 N-[4-(3,4-Dimethyl-benzylidene-hydrazinocarbonyl)-thiophen-3-yl]-3-[4-(2-hydroxy-ethyl)-piperazin-1-ylmethyl]-benzamide

The title compound 982 was produced in substantially the same manner as in Example 8.

¹H-NMR (CDCL₃, 400 MHz): δ 8.22-8.28 (1H, m), 7.95 (1H, s), 7.87 (1H, d, J=7.6 Hz), 7.30-7.56 (6H, m), 7.10-7.20 (1H, m), 3.57 (4H, s), 2.40-2.60 (10H, m), 2.28 (6H, s)

Mass spectrometric value (ESI-MS) 518, 519 (M−1) 542 (M+23)

Compound 983 N-[4-(4-Chloro-3-trifluoromethyl-benzylidene-hydrazinocarbonyl)-thiophen-3-yl]-3-[4-(2-hydroxy-ethyl)-piperazin-1-ylmethyl]-benzamide

The title compound 983 was produced in substantially the same manner as in Example 8.

¹H-NMR (CDCL₃, 400 MHz): δ 11.39 (1H, bs), 8.22 (1H, s), 7.82-8.00 (5H, m), 7.40-7.60 (4H, m), 3.55-3.62 (4H, m), 2.45-2.60 (10H, m)

Mass spectrometric value (ESI-MS) 592, 594 (M−1) 616 (M+23)

Compound 984 3-[4-(2-Hydroxy-ethyl)-piperazin-1-ylmethyl]-N-[4-(4-methoxy-benzylidene-hydrazinocarbonyl)-thiophen-3-yl]-benzamide

The title compound 984 was produced in substantially the same manner as in Example 8.

¹H-NMR (CDCL₃, 400 MHz): δ 11.86 (1H, bs), 11.51 (1H, bs), 8.25 (1H, d, J=3.4 Hz), 7.95 (1H, s), 7.87 (2H, d, J=7.3 Hz), 7.55-7.75 (2H, m), 7.49 (1H, d, J=7.3 Hz), 7.41 (1H, dd, J=7.7 Hz, J=7.7 Hz), 7.20-7.28 (1H, m), 6.85-7.30 (2H, m), 3.83 (3H, s), 3.58 (4H, s), 2.45-2.60 (10H, m)

Mass spectrometric value (ESI-MS) 520, 521 (M−1)

Compound 985 3-{[Bis-(2-hydroxy-propyl)-amino]-methyl}-N-[2-(3,4-dimethyl-benzylidene-hydrazinocarbonyl)-4-fluoro-phenyl]-benzamide

The title compound 985 was produced in substantially the same manner as in Example P.

¹H-NMR (CDCL₃, 400 MHz): δ 12.30-12.40 (1H, m), 8.55-8.65 (1H, m), 8.24-8.32 (1H, m), 8.14 (1H, s), 7.92-8.00 (1H, m), 7.56 (1H, s), 7.39 (1H, dd, J=7.3 Hz, J=7.3 Hz), 7.31 (1H, s), 7.16-7.28 (2H, m), 6.92-7.02 (1H, m), 6.76-6.86 (1H, m), 3.80-4.15 (4H, m), 3.55-3.65 (1H, m), 2.40-2.75 (4H, m), 2.14 (3H, s), 2.06 (3H, s), 1.10 (3H, d, J=6.4 Hz), 1.06 (3H, d, J=6.1 Hz)

Mass spectrometric value (ESI-MS) 533, 534 (M−1)

Compound 986 2-(3-{[Bis-(2-hydroxy-propyl)-amino]-methyl}-benzoylamino)-N-[2-(3,4-dimethyl-benzylidene-hydrazinocarbonyl)-4-fluoro-phenyl]-5-fluoro-benzamide

The title compound 986 was produced in substantially the same manner as in Example P.

¹H-NMR (CDCL₃, 400 MHz): δ 11.95-12.05 (1H, m), 11.16 (1H, bs), 10.93 (1H, bs), 8.75-8.85 (1H, m), 8.20-8.40 (1H, m), 7.20-8.10 (11H, m), 6.92-7.05 (1H, m), 3.70-3.95 (4H, m), 2.35-2.60 (4H, m), 2.12-2.21 (6H, m), 0.96-1.02 (6H, m)

Mass spectrometric value (ESI-MS) 670 (M−1)

Compound 987 3-{[Bis-(2-hydroxy-propyl)-amino]-methyl}-N-[4-fluoro-2-(3-fluoro-benzylidene-hydrazinocarbonyl)-phenyl]-benzamide

The title compound 987 was produced in substantially the same manner as in Example P.

¹H-NMR (CD₃OD, 400 MHz): δ 8.60-8.66 (1H, m), 8.35 (1H, s), 8.09 (1H, d, J=5.9 Hz), 7.95 (1H, d, J=8.0 Hz), 7.38-7.83 (7H, m), 7.15-7.28 (1H, m), 3.80-4.10 (4H, m), 2.58-2.75 (4H, m), 1.12 (3H, d, J=6.1 Hz), 1.11 (3H, d, J=6.4 Hz)

Mass spectrometric value (ESI-MS) 523, 524 (M−1) 547 (M+23)

Compound 988 2-(3-{[Bis-(2-hydroxy-propyl)-amino]-methyl}-benzoylamino)-5-fluoro-N-[4-fluoro-2-(3-fluoro-benzylidene-hydrazinocarbonyl)-phenyl]-benzamide

The title compound 988 was produced in substantially the same manner as in Example P.

¹H-NMR (CD₃OD, 400 MHz): δ 8.52-8.67 (1H, m), 8.32-8.40 (1H, m), 8.27 (1H, s), 7.36-8.08 (11H, m), 7.13-7.20 (1H, m), 3.60-3.95 (4H, m), 2.38-2.57 (4H, m), 1.02-1.10 (6H, m)

Mass spectrometric value (ESI-MS) 660, 661 (M−1) 684 (M+23)

Compound 989 3-{[Bis-(2-hydroxy-propyl)-amino]-methyl}-N-[4-fluoro-2-(4-methyl-benzylidene-hydrazinocarbonyl)-phenyl]-benzamide

The title compound 989 was produced in substantially the same manner as in Example P.

¹H-NMR (CD₃OD, 400 MHz): δ 8.60-8.67 (1H, m), 8.31 (1H, s), 8.02-8.07 (1H, m), 7.87-7.92 (1H, m), 7.75 (2H, d, J=7.8 Hz), 7.67 (1H, dd, J=2.7 Hz, J=9.0 Hz), 7.61 (1H, d, J=7.3 Hz), 7.50 (1H, dd, J=7.6 Hz, J=7.6 Hz), 7.36-7.43 (1H, m), 7.26 (2H, d, J=7.8 Hz), 3.65-3.95 (4H, m), 2.40-2.60 (4H, m), 2.38 (3H, s), 1.09 (3H, d, J=6.1 Hz), 1.08 (3H, d, J=6.1 Hz)

Mass spectrometric value (ESI-MS) 519, 520 (M−1) 543 (M+23)

Compound 990 3-{[Bis-(2-hydroxy-propyl)-amino]-methyl}-N-[4-fluoro-2-(4-methoxy-benzylidene-hydrazinocarbonyl)-phenyl]-benzamide

The title compound 990 was produced in substantially the same manner as in Example P.

¹H-NMR (CD₃OD, 400 MHz): δ 8.61-8.67 (1H, m), 8.29 (1H, s), 8.03-8.07 (1H, m), 7.87-7.92 (1H, m), 7.81 (2H, d, J=8.5 Hz), 7.66 (1H, dd, J=2.7 Hz, J=9.3 Hz), 7.61 (1H, d, J=7.1 Hz), 7.50 (1H, dd, J=7.6 Hz, J=7.6 Hz), 7.38-7.42 (1H, m), 6.99 (2H, d, J=8.8 Hz), 3.82-3.93 (4H, m), 3.84 (3H, s), 2.40-2.60 (4H, m), 1.09 (3H, d, J=6.4 Hz), 1.08 (3H, d, J=6.1 Hz)

Mass spectrometric value (ESI-MS) 535, 536, 537 (M−1) 559 (M+23)

Compound 991 N-[5-Tert-butyl-2-(3,4-dimethyl-benzylidene-hydrazinocarbonyl)-thiophen-3-yl]-3-[4-(2-hydroxy-ethyl)-piperazin-1-ylmethyl]-benzamide

The title compound 991 was produced in substantially the same manner as in Example 8.

¹H-NMR (CD₃OD, 400 MHz): δ 8.15 (1H, s), 7.99 (1H, s), 7.88-7.97 (2H, m), 7.70 (1H, s), 7.60 (1H, d, J=7.3 Hz), 7.44-7.55 (2H, m), 7.20 (1H, d, J=7.8 Hz), 3.64-3.70 (4H, m), 2.53-2.70 (10H, m), 2.32 (3H, s), 2.31 (3H, s), 1.50 (9H, s)

Mass spectrometric value (ESI-MS) 574, 575, 576 (M−1)

Compound 992 3-{[Bis-(2-hydroxy-propyl)-amino]-methyl}-N-[2-(3-fluoro-benzylidene-hydrazinocarbonyl)-thiophen-3-yl]-benzamide

The title compound 992 was produced in substantially the same manner as in Example 8.

¹H-NMR (CD₃OD, 400 MHz): δ 8.26-8.34 (1H, m), 7.15-8.13 (10H, m), 3.80-4.08 (4H, m), 2.55-2.70 (4H, m), 1.13 (3H, d, J=6.1 Hz), 1.12 (3H, d, J=6.1 Hz)

Mass spectrometric value (ESI-MS) 511, 512, 513 (M−1)

Compound 993 3-{[Bis-(2-hydroxy-propyl)-amino]-methyl}-N-[2-(4-chloro-3-trifluoromethyl-benzylidene-hydrazinocarbonyl)-thiophen-3-yl]-benzamide

The title compound 993 was produced in substantially the same manner as in Example 8.

¹H-NMR (CD₃OD, 400 MHz): δ 8.19-8.35 (2H, m), 8.00-8.09 (3H, m), 7.83-7.94 (2H, m), 7.68 (1H, d, J=8.5 Hz), 7.58-7.65 (1H, m), 7.47-7.55 (1H, m), 3.65-3.98 (4H, m), 2.45-2.65 (4H, m), 1.03-1.14 (6H, m)

Mass spectrometric value (ESI-MS) 595, 597, 598 (M−1)

Compound 995 3-Diethylaminomethyl-N-[2-(3-fluoro-benzylidene-hydrazinocarbonyl)-thiophen-3-yl]-benzamide

The title compound 995 was produced in substantially the same manner as in Example 8.

¹H-NMR (CDCL₃, 400 MHz): δ 12.38 (1H, bs), 9.08 (1H, s), 8.39 (1H, d, J=5.6 Hz), 7.95 (1H, s), 7.84 (1H, d, J=8.1 Hz), 7.74 (1H, bs), 7.65 (1H, bs), 7.51 (1H, d, J=7.6 Hz), 7.30-7.46 (4H, m), 7.02-7.10 (1H, m), 3.59 (2H, s), 2.48 (4H, q, J=7.1 Hz), 0.99 (6H, t, J=7.1 Hz)

Mass spectrometric value (ESI-MS) 451, 452, 453 (M−1)

Compound 996 3-{[Bis-(2-hydroxy-propyl)-amino]-methyl}-N-{4-bromo-2-[1-(3-fluoro-phenyl)-ethylidene-hydrazinocarbonyl]-phenyl}-benzamide

The title compound 996 was produced in substantially the same manner as in Example 8.

Mass spectrometric value (ESI-MS) 599 (M−1)

Compound 997 3-{[Bis-(2-hydroxy-propyl)-amino]-methyl}-N-{4-bromo-2-[1-(4-methoxy-phenyl)-ethylidene-hydrazinocarbonyl]-phenyl}-benzamide

The title compound 997 was produced in substantially the same manner as in Example 8.

Mass spectrometric value (ESI-MS) 609, 611 (M−1)

Compound 998 3-{[Bis-(2-hydroxy-propyl)-amino]-methyl}-N-{4-chloro-2-[4-(3-dimethylamino-propoxy)-benzylidene-hydrazinocarbonyl]-phenyl}-benzamide

The title compound 998 was produced in substantially the same manner as in Example 8.

¹H-NMR (CD₃OD, 400 MHz): δ 8.67-8.70 (1H, m), 8.30 (1H, s), 8.06 (1H, s), 7.88-7.94 (2H, m), 7.79-7.84 (2H, m), 7.59-7.64 (2H, m), 7.47-7.54 (1H, m), 6.96-7.02 (2H, m), 4.08 (2H, t, J=6.1 Hz), 3.82-3.95 (4H, m), 2.40-2.60 (6H, m), 2.30-2.34 (6H, s), 1.95-2.05 (2H, m), 1.09 (3H, d, J=6.4 Hz), 1.08 (3H, d, J=6.1 Hz)

Mass spectrometric value (ESI-MS) 622 (M−1)

Compound 999 N-{4-Chloro-2-[4-(3-dimethylamino-propoxy)-benzylidene-hydrazinocarbonyl]-phenyl}-3-{[(2-diethylamino-ethyl)-methyl-amino]-methyl}-benzamide

The title compound 999 was produced in substantially the same manner as in Example 8.

¹H-NMR (CDCL₃, 400 MHz): δ 11.58 (1H, bs), 8.54 (1H, d, J=9.3 Hz), 8.26 (1H, s), 7.95 (1H, s), 7.86 (1H, d, J=7.8 Hz), 7.72 (2H, d, J=7.6 Hz), 7.50-7.56 (2H, m), 7.38-7.45 (2H, m), 6.91 (2H, d, J=8.8 Hz), 4.03 (2H, t, J=6.5 Hz), 3.60 (2H, s), 2.47-2.65 (8H, m), 2.43 (2H, t, J=7.2 Hz), 2.23 (6H, s), 2.22 (3H, s), 1.94 (2H, tt, J=6.8 Hz, J=6.8 Hz), 0.99 (6H, t, J=7.2 Hz)

Mass spectrometric value (ESI-MS) 619, 620 (M−1)

Compound 1000 (4-{[5-Chloro-2-(3-{[(2-diethylamino-ethyl)-methyl-amino]-methyl}-benzoylamino)-benzoyl]-hydrazinomethyl}-phenoxy)-acetic acid

The title compound 1000 was produced in substantially the same manner as in Example 8.

¹H-NMR (CD₃OD, 400 MHz): δ 8.62 (1H, d, J=9.0 Hz), 8.29 (1H, s), 7.89-8.00 (3H, m), 7.74 (2H, d, J=8.8 Hz), 7.51-7.65 (3H, m), 6.98 (2H, d, J=8.8 Hz), 4.44 (2H, s), 3.72 (2H, s), 3.21 (2H, t, J=6.1 Hz), 3.07 (4H, q, J=7.3 Hz), 2.74 (2H, t, J=6.1 Hz), 2.32 (3H, s), 1.20 (6H, t, J=7.3 Hz)

Mass spectrometric value (ESI-MS) 592, 594 (M−1) 618, 619 (M+23)

Compound 1001 3-{[(2-Diethylamino-ethyl)-methyl-amino]-methyl}-N-[3-(4-trifluoromethoxy-benzylidene-hydrazinocarbonyl)-4,5,6,7-tetrahydro-benzo[b]thiophen-2-yl]-benzamide

The title compound 1001 was produced in substantially the same manner as in Example 8.

¹H-NMR (CD₃OD, 400 MHz): δ 8.30 (1H, s), 7.90-8.03 (4H, m), 7.58-7.64 (1H, m), 7.50-7.57 (1H, m), 7.32-7.38 (2H, m), 3.67 (2H, s), 2.88 (4H, bs), 2.72-2.82 (6H, m), 2.58-2.66 (2H, m), 2.29 (3H, s), 1.83-1.95 (41-1, m), 1.09 (6H, t, J=7.2 Hz)

Mass spectrometric value (ESI-MS) 628, 629, 630 (M−1)

Compound 1002 3-{[(2-Diethylamino-ethyl)-methyl-amino]-methyl}-N-{3-[4-(2-hydroxy-ethoxy)-benzylidene-hydrazinocarbonyl]-4,5,6,7-tetrahydro-benzo[b]thiophen-2-yl}-benzamide

The title compound 1002 was produced in substantially the same manner as in Example 8.

¹H-NMR (CD₃OD, 400 MHz): δ 8.22 (1H, s), 7.70-8.00 (4H, m), 7.58-7.69 (1H, m), 7.50-7.57 (1H, m), 7.02 (2H, d, J=8.8 Hz), 4.10 (2H, t, J=4.6 Hz), 3.89 (2H, t, J=4.8 Hz), 3.67 (2H, s), 2.80-2.90 (4H, m), 2.66-2.78 (6H, m), 2.60 (2H, t, J=7.0 Hz), 2.28 (3H, s), 1.80-1.95 (4H, m), 1.08 (6H, t, J=7.2 Hz)

Mass spectrometric value (ESI-MS) 604, 605, 606 (M−1)

Compound 1003 3-{[(2-Diethylamino-ethyl)-methyl-amino]-methyl}-N-{3-[1-(3-fluoro-phenyl)-ethylidene-hydrazinocarbonyl]-4,5,6,7-tetrahydro-benzo[b]thiophen-2-yl}-benzamide

The title compound 1003 was produced in substantially the same manner as in Example 8.

¹H-NMR (CD₃OD, 400 MHz): δ 7.85-7.98 (2H, m), 7.68-7.80 (2H, m), 7.47-7.62 (2H, m), 7.40-7.47 (1H, m), 7.10-7.20 (1H, m), 3.66 (2H, s), 2.95 (2H, bs), 2.55-2.85 (10H, m), 2.35 (3H, s), 2.28 (3H, s), 1.87-1.93 (4H, m), 1.05 (6H, t, J=7.2 Hz)

Mass spectrometric value (ESI-MS) 576, 577, 578 (M−1) 600, 601 (M+23)

Compound 1004 Quinoxaline-2-carboxylic acid [4-chloro-2-(3-fluoro-benzylidene-hydrazinocarbonyl)-phenyl]-amide

The title compound 1004 was produced in substantially the same manner as in Example 1).

¹H-NMR (DMSO-d₆, 400 MHz): δ 12.65 (1H, s), 12.30 (1H, s), 9.61 (1H, s), 8.75 (1H, d, J=8.8 Hz), 8.47 (1H, s), 8.20-8.33 (2H, m), 8.00-8.10 (3H, m), 7.79 (1H, d, J=8.6 Hz), 7.50-7.67 (3H, m), 7.28-7.38 (1H, m)

Mass spectrometric value (ESI-MS) 446, 448 (M−1)

Compound 1005 Quinoxaline-2-carboxylic acid [4-chloro-2-(3,4-dimethyl-benzylidene-hydrazinocarbonyl)-phenyl]-amide

The title compound 1005 was produced in substantially the same manner as in Example 1).

¹H-NMR (CDCL₃, 400 MHz): δ 12.52 (1H, bs), 9.68 (1H, s), 9.46 (1H, bs), 8.70-8.80 (1H, bs), 8.12-8.20 (2H, m), 7.82-7.88 (3H, m), 7.40-7.70 (3H, m), 7.12 (1H, d, J=7.8 Hz), 2.26 (3H, s), 2.20 (3H, s)

Mass spectrometric value (ESI-MS) 456, 458 (M−1)

Compound 1006 Quinoxaline-2-carboxylic acid[4-chloro-2-(4-chloro-3-trifluoromethyl-benzylidene-hydrazinocarbonyl)-phenyl]-amide

The title compound 1006 was produced in substantially the same manner as in Example 1).

¹H-NMR (DMSO-d₆, 400 MHz): δ 12.57 (1H, s), 12.44 (1H, s), 9.61 (1H, s), 8.73 (1H, d, J=8.8 Hz), 8.51 (1H, s), 8.20-8.32 (3H, m), 7.98-8.14 (4H, m), 7.85 (1H, d, J=8.5 Hz), 7.79 (1H, d, J=9.0 Hz)

Mass spectrometric value (ESI-MS) 530, 532 (M−1)

Compound 1007 N-[4-Chloro-2-(3-fluoro-benzylidene-hydrazinocarbonyl)-phenyl]-3-(2,3-dihydroxy-propylsulfanyl methyl)-benzamide

The title compound 1007 was produced in substantially the same manner as in Example 8.

¹H-NMR (CD₃OD, 400 MHz): δ 8.64 (1H, d, J=8.8 Hz), 8.36 (1H, s), 7.97 (1H, s), 7.94 (1H, d, J=2.4 Hz), 7.87 (1H, d, J=7.8 Hz), 7.71 (1H, d, J=9.5 Hz), 7.60-7.66 (3H, m), 7.40-7.54 (2H, m), 7.15-7.25 (1H, m), 3.90 (2H, s), 3.70-3.80 (1H, m), 3.48-3.60 (2H, m), 2.64 (1H, dd, J=5.6 Hz, J=13.7 Hz), 2.51 (1H, dd, J=6.8 Hz, J=13.4 Hz)

Mass spectrometric value (ESI-MS) 514, 516 (M−1)

Compound 1008 N-[4-Chloro-2-(4-methyl-benzylidene-hydrazinocarbonyl)-phenyl]-3-(2,3-dihydroxy-propylsulfanylmethyl)-benzamide

The title compound 1008 was produced in substantially the same manner as in Example 8.

¹H-NMR (CD₃OD, 400 MHz): δ 8.65 (1H, d, J=9.0 Hz), 8.36 (1H, s), 7.97 (1H, s), 7.93 (1H, d, J=2.5 Hz), 7.87 (1H, d, J=7.6 Hz), 7.74 (2H, d, J=8.3 Hz), 7.62 (2H, dd, J=2.4 Hz, J=9.0 Hz), 7.51 (1H, dd, J=7.6 Hz, J=7.6 Hz), 7.27 (2H, d, J=8.1 Hz), 3.90 (2H, s), 3.70-3.80 (1H, m), 3.50-3.61 (2H, m), 2.63 (1H, dd, J=5.6 Hz, J=13.6 Hz), 2.50 (1H, dd, J=6.8 Hz, 13.6 Hz), 2.38 (3H, s)

Mass spectrometric value (ESI-MS) 510, 512, 513 (M−1)

Compound 1009 N-[4-Chloro-2-(3,4-dimethyl-benzylidene-hydrazinocarbonyl)-phenyl]-3-(2,3-dihydroxy-propylsulfanylmethyl)-benzamide

The title compound 1009 was produced in substantially the same manner as in Example 8.

¹H-NMR (CD₃OD, 400 MHz): δ 8.66 (1H, d, J=9.0 Hz), 8.31 (1H, s), 7.97 (1H, bs), 7.93 (1H, d, J=2.4 Hz), 7.87 (1H, bs), 7.60-7.69 (3H, m), 7.48-7.58 (2H, m), 7.15-7.25 (1H, m), 3.90 (2H, s), 3.70-3.80 (1H, m), 3.50-3.61 (2H, m), 2.63 (1H, dd, J=5.4 Hz, J=13.7 Hz), 2.50 (1H, dd, J=6.8 Hz, J=13.6 Hz), 2.32 (3H, s), 2.31 (3H, s)

Mass spectrometric value (ESI-MS) 524, 526, 529 (M−1)

Compound 1010 N-[4-Chloro-2-(4-chloro-3-trifluoromethyl-benzylidene-hydrazinocarbonyl)-phenyl]-3-(2,3-dihydroxy-propylsulfanylmethyl)-benzamide

The title compound 1010 was produced in substantially the same manner as in Example 8.

¹H-NMR (CD₃OD, 400 MHz): δ 8.63 (1H, d, J=8.8 Hz), 8.39 (1H, s), 8.30-8.34 (1H, m), 8.08 (1H, d, J=8.3 Hz), 7.96 (1H, bs), 7.94 (1H, d, J=2.4 Hz), 7.85-7.90 (1H, m), 7.70 (1H, d, J=8.3 Hz), 7.60-7.67 (2H, m), 7.68-7.55 (1H, m), 3.89 (2H, s), 3.70-3.80 (1H, m), 3.48-3.60 (2H, m), 2.64 (1H, dd, J=5.6 Hz, J=13.7 Hz), 2.50 (1H, dd, J=7.1 Hz, J=13.7 Hz)

Mass spectrometric value (ESI-MS) 598, 600, 601, 603 (M−1)

Compound 1011 N-[4-Chloro-2-(4-methoxy-benzyl idene-hydrazinocarbonyl)-phenyl]-3-(2,3-dihydroxy-propylsulfanylmethyl)-benzamide

The title compound 1011 was produced in substantially the same manner as in Example 8.

¹H-NMR (CD₃OD, 400 MHz): δ 8.66 (1H, d, J=9.0 Hz), 8.31 (1H, s), 7.95-7.98 (1H, m), 7.92 (1H, d, J=2.4 Hz), 7.86-7.90 (1H, m), 7.81 (2H, d, J=8.8 Hz), 7.60-7.65 (2H, m), 7.51 (1H, dd, J=7.7 Hz, J=7.7 Hz), 7.00 (2H, d, J=8.8 Hz), 3.90 (2H, s), 3.85 (3H, s), 3.70-3.80 (1H, m), 3.50-3.61 (2H, m), 2.63 (1H, dd, J=5.6 Hz, J=13.6 Hz), 2.51 (1H, dd, J=6.8 Hz, J=13.6 Hz)

Mass spectrometric value (ESI-MS) 529, 530, 531 (M−1)

Compound 1012 N-[4-Chloro-2-(4-trifluoromethoxy-benzylidene-hydrazinocarbonyl)-phenyl]-3-(2,3-dihydroxy-propylsulfanylmethyl)-benzamide

The title compound 1012 was produced in substantially the same manner as in Example 8.

¹H-NMR (CD₃OD, 400 MHz): δ 8.64 (1H, d, J=9.0 Hz), 8.39 (1H, s), 7.93-8.01 (4H, m), 7.85-7.90 (1H, m), 7.60-7.67 (2H, m), 7.51 (1H, dd, J=7.7 Hz, J=7.7 Hz), 7.36 (2H, d, J=8.1 Hz), 3.90 (2H, s), 3.70-3.80 (1H, m), 3.50-3.60 (2H, m), 2.63 (1H, dd, J=5.8 Hz, J=13.6 Hz), 2.51 (1H, dd, J=6.8 Hz, J=13.6 Hz)

Mass spectrometric value (ESI-MS) 580, 582, 583 (M−1)

Example Q Compound 1013 3-(2,3-Dihydroxy-propylsulfanylmethyl)-N-[2-(3-fluoro-benzylidene-hydrazinocarbonyl)-4,5-bis-(2-methoxy-ethoxy)-phenyl]-benzamide

3,4-Dihydroxy-benzoic acid ethyl ester (compound A′) (2.0 g) was dissolved in acetone (20 ml). Potassium carbonate (4.3 g) and 1-bromo-2-methoxy-ethane (compound D) (5 ml) were added to the solution at room temperature, and the mixture was then stirred at 70° C. for 24 hr. After the completion of the reaction, the reaction solution was allowed to stand for cooling at room temperature, and the reaction system was concentrated under the reduced pressure. Distilled water was added to the residue, and the mixture was then subjected to separatory extraction with chloroform. The organic layer was washed with saturated brine, was dried over sodium sulfate, and was then concentrated under the reduced pressure. The residue was purified by column chromatography using a hexane-acetone system to give 3,4-bis-(2-methoxy-ethoxy)-benzoic acid ethyl ester (3.06 g, yield 93%).

3,4-Bis-(2-methoxy-ethoxy)-benzoic acid ethyl ester (200 mg) produced by the above process was dissolved in acetic acid (200 μl). Fuming nitric acid (200 μl) was added dropwise to the solution at 0° C., and the mixture was then stirred at room temperature for one hr. After the completion of the reaction, the reaction system was added dropwise to distilled water (500 μl) cooled to 0° C., and the mixture was then neutralized with a saturated aqueous sodium hydrogencarbonate solution, and was further subjected to separatory extraction with ethyl acetate. The organic layer was washed with saturated brine, was dried over sodium sulfate, and was then concentrated under the reduced pressure. The residue was purified by column chromatography eluted with a hexane-acetone system to give 4,5-bis-(2-methoxy-ethoxy)-2-nitro-benzoic acid ethyl ester as a useful intermediate (220 mg, yield 96%).

Subsequently, 4,5-bis-(2-methoxy-ethoxy)-2-nitro-benzoic acid ethyl ester (3.0 mg) produced by the above process was dissolved in methanol, and platinum oxide (250 mg) was added to the solution at room temperature. The air in the reaction system was replaced by hydrogen, and the mixture was then stirred for one hr. After the completion of the reaction, the atmosphere in the reaction system was replaced by nitrogen. The reaction solution was filtered through Celite to remove platinum oxide. The filtrate was then concentrated under the reduced pressure. The residue was purified by column chromatography eluted with a hexane-acetone system to give 2-amino-4,5-bis-(2-methoxy-ethoxy)-benzoic acid ethyl ester (compound A) (2.5 g, yield 92%).

2-Amino-4,5-bis-(2-methoxy-ethoxy)-benzoic acid ethyl ester (compound A) (2.5 g) produced by the above process was dissolved in anhydrous methylene chloride (40 ml). Pyridine (1.4 ml) and 3-(chloromethyl)-benzoyl chloride (compound B) (1.3 ml) were added dropwise to the solution at 0° C., and the mixture was stirred at room temperature for 30 min. After the completion of the reaction, distilled water was added thereto at room temperature, and the mixture was then subjected to separatory extraction with chloroform. The organic layer was washed with saturated brine, was dried over sodium sulfate, and was then concentrated under the reduced pressure. The residue was purified by column chromatography using a hexane-acetone system to give 2-(3-chloromethylbenzoylamino)-4,5-bis-(2-methoxy-ethoxy)-benzoic acid ethyl ester (2.3 g, yield 62%).

Subsequently, 2-(3-chloromethyl-benzoylamino)-4,5-bis-(2-methoxy-ethoxy)-benzoic acid ethyl ester (1.1 g) was dissolved in anhydrous methylene chloride (20 ml). Triethylamine (800 μl) and 3-mercapto-1,2-propanediol (compound B′) (600 μl) were added dropwise to the solution at room temperature, and the mixture was stirred at that temperature for 36 hr. After the completion of the reaction, distilled water was added thereto at room temperature, and the mixture was then subjected to separatory extraction with chloroform. The organic layer was washed with saturated brine, was dried over sodium sulfate, and was then concentrated under the reduced pressure. The residue was purified by column chromatography eluted with a chloroform-methanol system to give 2-[3-(2,3-dihydroxy-propylsulfanylmethyl)-benzoylamino]-4,5-bis-(2-methoxy-ethoxy)-benzoic acid ethyl ester (970 mg, yield 77%)_(.)

2-[3-(2,3-Dihydroxy-propylsulfanylmethyl)-benzoylamino]-4,5-bis-(2-methoxy-ethoxy)-benzoic acid ethyl ester (970 mg) produced by the above process was dissolved in ethanol (10 ml). Hydrazine monohydrate (1 ml) was added dropwise to the solution at room temperature, and the mixture was then stirred at that temperature for 36 hr. After the completion of the reaction, the reaction system was then concentrated under the reduced pressure, and the residue was purified by column chromatography eluted with a chloroform-methanol system to give 3-(2,3-dihydroxy-propylsulfanylmethyl)-N-[2-hydrazinocarbonyl-4,5-bis-(2-methoxy-ethoxy)-phenyl]-benzamide (780 mg, yield 83%).

Subsequently, 3-(2,3-dihydroxy-propylsulfanylmethyl)-N-[2-hydrazinocarbonyl-4,5-bis-(2-methoxy-ethoxy)-phenyl]-benzamide (55 mg) produced by the above process was dissolved in anhydrous toluene (1 ml), 3-fluorobenzaldehyde (compound C) (50 μl) was added dropwise to the solution at room temperature, and the mixture was then stirred at that temperature for one hr. After the completion of the reaction, the reaction system was concentrated under the reduced pressure, and the residue was purified by column chromatography eluted with a chloroform-methanol system to give the title compound 1013 (66 mg, yield 100%).

¹H-NMR (CDCL₃, 400 MHz): δ 12.00 (1H, bs), 10.14 (1H, bs), 8.50 (1H, s), 8.16 (1H, s), 7.93 (1H, d, J=7.6 Hz), 7.60-7.78 (2H, m), 7.24-7.57 (5H, m), 7.00-7.10 (1H, m), 4.20-4.28 (2H, m), 4.00-4.10 (3H, m), 3.80-3.88 (3H, m), 3.75-3.80 (2H, m), 3.60-3.72 (3H, m), 3.41 (3H, s), 3.38 (3H, s), 2.60 (2H, d, J=6.6 Hz)

Mass spectrometric value (ESI-MS) 628, 629 (M−1)

Compound 1014 N-[4,5-Bis-(2-methoxy-ethoxy)-2-(4-methyl-benzylidene-hydrazinocarbonyl)-phenyl]-3-(2,3-dihydroxy-propylsulfanylmethyl)-benzamide

The title compound 1014 was produced in substantially the same manner as in Example Q.

¹H-NMR (CDCL₃, 400 MHz): δ 12.06 (1H, bs), 9.84 (1H, bs), 8.54 (1H, s), 8.13 (1H, bs), 7.90-7.96 (2H, m), 7.77 (1H, s), 7.65-7.74 (2H, m), 7.45-7.55 (3H, m), 7.18 (1H, d, J=7.8 Hz), 4.22-4.28 (2H, m), 4.00-4.14 (3H, m), 3.80-3.85 (3H, m), 3.75-3.80 (2H, m), 3.62-3.70 (3H, m), 3.41 (3H, s), 3.40 (3H, s), 2.58 (2H, d, J=6.4 Hz), 2.34 (3H, s)

Mass spectrometric value (ESI-MS) 624, 625 (M−1)

Compound 1015 3-(2,3-Dihydroxy-propylsulfanylmethyl)-N-[2-(3,4-dimethyl-benzylidene-hydrazinocarbonyl)-4,5-bis-(2-methoxy-ethoxy)-phenyl]-benzamide

The title compound 1015 was produced in substantially the same manner as in Example Q.

¹H-NMR (CDCL₃, 400 MHz): δ 12.08 (1H, bs), 9.95 (1H, bs), 8.53 (1H, s), 8.11 (1H, bs), 7.93 (1H, d, J=7.6 Hz), 7.76-7.83 (2H, m), 7.60 (1H, bs), 7.45-7.57 (3H, m), 7.11 (1H, d, J=7.8 Hz), 4.23-4.28 (2H, m), 4.07-4.12 (1H, m), 3.82-3.90 (3H, m), 3.75-3.80 (2H, m), 3.60-3.70 (3H, m), 3.41 (3H, s), 3.39 (3H, s), 2.59 (2H, d, J=6.6 Hz), 2.29 (2H, d, J=7.4 Hz), 2.24 (3H, s), 2.23 (3H, s)

Mass spectrometric value (ESI-MS) 638 (M−1)

Compound 1016 N-[2-(4-Chloro-3-trifluoromethyl-benzylidene-hydrazinocarbonyl)-4,5-bis-(2-methoxy-ethoxy)-phenyl]-3-(2,3-dihydroxy-propylsulfanylmethyl)-benzamide

The title compound 1016 was produced in substantially the same manner as in Example Q.

¹H-NMR (CDCL₃, 400 MHz): δ 12.07 (1H, s), 10.69 (1H, s), 8.40 (1H, s), 8.15 (1H, s), 8.07 (1H, s), 7.93 (1H, d, J=7.1 Hz), 7.73-7.77 (1H, m), 7.71 (1H, s), 7.46-7.56 (2H, m), 7.38 (1H, d, J=8.3 Hz), 7.33 (1H, s), 4.60 (1H, bs), 4.18-4.23 (2H, m), 3.97-4.08 (3H, m), 3.74-3.95 (5H, m), 3.62-3.72 (1H, m), 3.58 (2H, t, J=9.0 Hz), 3.40 (3H, s), 3.37 (3H, s), 2.58-2.72 (2H, m)

Mass spectrometric value (ESI-MS) 712, 715 (M−1)

Example R Compound 1017 3-(2,3-Dihydroxy-propylsulfanylmethyl)-N-[2-(3-fluoro-benzylidene-hydrazinocarbonyl)-4-methoxy-phenyl]-benzamide

5-Methoxy-2-nitro-benzoic acid (2.5 g) was dissolved in N,N-dimethylformamide (compound A′) (40 ml). Potassium carbonate (4.5 g) and methyl iodide (2.5 ml) were added to the solution at room temperature, and the mixture was then stirred at that temperature for 30 min. After the completion of the reaction, distilled water was added thereto at room temperature, and the mixture was then subjected to separatory extraction with ethyl acetate. The organic layer was washed with saturated brine, was dried over sodium sulfate, and was then concentrated under the reduced pressure. The residue was purified by column chromatography eluted with a hexane-acetone system to give 5-methoxy-2-nitrobenzoic acid methyl ester (2.7 g, yield 100%).

Subsequently, 5-methoxy-2-nitro-benzoic acid methyl ester (2.7 g) produced by the above process was dissolved in methanol (20 ml), and platinum oxide (180 mg) was added to the solution at room temperature. The air in the reaction system was replaced by hydrogen, the mixture was then stirred at that temperature for 5 hr. After the completion of the reaction, the atmosphere in the reaction system was replaced by nitrogen, and the reaction solution was then filtered through Celite to remove platinum oxide. The filtrate was then concentrated under the reduced pressure. The residue was purified by column chromatography eluted with a hexane-acetone system to give 2-amino-5-methoxy-benzoic acid methyl ester (compound A) (2.2 g, yield 96%).

2-Amino-5-methoxy-benzoic acid methyl ester (compound A) (2.2 g) produced by the above process was dissolved in anhydrous methylene chloride (40 ml), pyridine (1.5 ml) and 3-(chloromethyl)benzoyl chloride (compound B) (2.1 ml) was added dropwise to the solution at 0° C., and the mixture was then stirred at room temperature for 15 min. After the completion of the reaction, distilled water was added thereto at room temperature, and the mixture was then subjected to separatory extraction with chloroform. The organic layer was washed with saturated brine, was dried over sodium sulfate, and was then concentrated under the reduced pressure to precipitate crystals. The crude crystals were collected by Kiriyama Rohto and was washed with ether to give 2-(3-chloromethyl-benzoylamino)-5-methoxybenzoic acid methyl ester (3.0 g, yield 75%).

Subsequently, 2-(3-chloromethyl-benzoylamino)-5-methoxy-benzoic acid methyl ester (1.0 g) produced by the above process was dissolved in anhydrous methylene chloride (10 ml). Triethylamine (1 ml) and 3-mercapto-1,2-propanediol (compound B′) (1 ml) were added dropwise to the solution at room temperature, and the mixture was then stirred at that temperature for 36 hr. After the completion of the reaction, distilled water was added thereto at room temperature, and the mixture was then subjected to separatory extraction with chloroform. The organic layer was washed with saturated brine, was dried over sodium sulfate, and was then concentrated under the reduced pressure.

The residue was purified by column chromatography eluted with a chloroform-methanol system to give 2-[3-(2,3-dihydroxy-propanesulfanylmethyl)-benzoylamino]-5-methoxy-benzoic acid methyl ester as a useful intermediate (1.2 g, yield 100%).

2-[3-(2,3-Dihydroxy-propanesulfanylmethyl)-benzoylamino]-5-methoxybenzoic acid methyl ester (1.2 g) produced by the above process was dissolved in ethanol (20 ml). Hydrazine monohydrate (1.3 ml) was added dropwise to the solution at room temperature, and the mixture was then stirred at that temperature for 12 hr. After the completion of the reaction, the reaction system was then concentrated under the reduced pressure, and the residue was purified by column chromatography eluted with a chloroform-methanol system to give 3-(2,3-dihydroxy-propylsulfanyl methyl)-N-(2-hydrazinocarbonyl-4-methoxyphenyl)benzamide (840 mg, yield 65%).

Subsequently, 3-(2,3-dihydroxy-propylsulfanylmethyl)-N-(2-hydrazinocarbonyl-4-methoxy-phenyl)benzamide (61 mg) produced by the above process was dissolved in anhydrous toluene (1.5 ml). 3-Fluorobenzaldehyde (compound C) (50 μl) was added dropwise to the solution at room temperature, and the mixture was then stirred at 40° C. for 12 hr. After the completion of the reaction, the reaction system was concentrated under the reduced pressure, and the residue was purified by column chromatography eluted with a chloroform-methanol system to give the title compound 1017 (59 mg, 77%).

¹H-NMR (CD₃OD, 400 MHz): δ 8.42 (1H, d, J=9.3 Hz), 8.34 (1H, s), 7.95 (1H, s), 7.85 (1H, d, J=7.8 Hz), 7.70 (1H, d, J=10.2 Hz), 7.58-7.62 (2H, m), 7.40-7.52 (3H, m), 7.12-7.25 (2H, m), 3.90 (3H, s), 3.89 (2H, s), 3.70-3.78 (1H, m), 3.48-3.60 (2H, m), 2.63 (1H, dd, J=5.6 Hz, J=13.7 Hz), 2.50 (1H, dd, J=6.8 Hz, J=13.4 Hz)

Mass spectrometric value (ESI-MS) 510, 511 (M−1) 534 (M+23)

Compound 1018 3-(2,3-Dihydroxy-propylsulfanylmethyl)-N-[4-methoxy-2-(4-methyl-benzylidene-hydrazinocarbonyl)-phenyl]-benzamide

The title compound 1018 was produced in substantially the same manner as in Example R.

¹H-NMR (CD₃OD, 400 MHz): δ 8.44 (1H, d, J=9.0 Hz), 8.32 (1H, s), 7.95 (1H, s), 7.83-7.89 (1H, m), 7.74 (2H, d, J=8.1 Hz), 7.60 (1H, d, J=7.8 Hz), 7.49 (1H, dd, J=7.6 Hz, J=7.6 Hz), 7.41 (1H, d, J=2.9 Hz), 7.19-7.29 (3H, m), 3.90 (3H, s), 3.89 (2H, s), 3.70-3.78 (1H, m), 3.48-3.61 (2H, m), 2.63 (1H, dd, J=5.9 Hz, J=13.7 Hz), 2.50 (1H, dd, J=6.8 Hz, J=13.7 Hz), 2.38 (3H, s)

Mass spectrometric value (ESI-MS) 506, 507 (M−1)

Compound 1019 3-(2,3-Dihydroxy-propylsulfanylmethyl)-N-[2-(3,4-dimethyl-benzylidene-hydrazinocarbonyl)-4-methoxy-phenyl]-benzamide

The title compound 1019 was produced in substantially the same manner as in Example R.

¹H-NMR (CD₃OD, 400 MHz): δ 8.44 (1H, d, J=9.0 Hz), 8.29 (1H, s), 7.95 (1H, s), 7.86 (1H, d, J=7.6 Hz), 7.66 (1H, s), 7.60 (1H, d, J=7.8 Hz), 7.54 (1H, d, J=7.3 Hz), 7.49 (1H, dd, J=7.9 Hz, J=7.9 Hz), 7.41 (1H, d, J=2.9 Hz), 7.15-7.25 (2H, m), 3.90 (3H, s), 3.89 (2H, s), 3.70-3.80 (1H, m), 3.49-3.60 (2H, m), 2.63 (1H, dd, J=5.6 Hz, J=13.7 Hz), 2.50 (1H, dd, J=7.1 Hz, J=13.7 Hz), 2.31 (3H, s), 2.30 (3H, s)

Mass spectrometric value (ESI-MS) 520 (M−1)

Compound 1020 N-[2-(4-Chloro-3-trifluoromethyl-benzylidene-hydrazinocarbonyl)-4-methoxy-phenyl]-3-(2,3-dihydroxy-propylsulfanyl-methyl)-benzamide

The title compound 1020 was produced in substantially the same manner as in Example R.

¹H-NMR (CD₃OD, 400 MHz): δ 8.41 (1H, d, J=9.3 Hz), 8.38 (1H, s), 8.32 (1H, bs), 8.05-8.15 (1H, m), 7.94 (1H, bs), 7.83-7.88 (1H, m), 7.69 (1H, d, J=8.3 Hz), 7.58-7.63 (1H, m), 7.47-7.52 (1H, m), 7.42 (1H, d, J=2.9 Hz), 7.20-7.25 (1H, m), 3.90 (3H, s), 3.89 (2H, s), 3.75-3.82 (1H, m), 3.45-3.60 (2H, m), 2.60-2.67 (1H, m), 2.45-2.54 (1H, m)

Mass spectrometric value (ESI-MS) 594, 596, 597 (M−1)

Compound 1021 3-(2,3-Dihydroxy-propylsulfanylmethyl)-N-[4-methoxy-2-(4-methoxy-benzylidene-hydrazinocarbonyl)-phenyl]-benzamide

The title compound 1021 was produced in substantially the same manner as in Example R.

¹H-NMR (CD₃OD, 400 MHz): δ 8.44 (1H, d, J=9.3 Hz), 8.29 (1H, s), 7.95 (1H, bs), 7.86 (1H, d, J=7.6 Hz), 7.80 (2H, d, J=8.8 Hz), 7.60 (1H, d, J=7.8 Hz), 7.49 (1H, dd, J=7.7 Hz, J=7.7 Hz), 7.40 (1H, d, J=2.9 Hz), 7.21 (1H, dd, J=2.9 Hz, J=9.3 Hz), 6.99 (2H, d, J=8.8 Hz), 3.90 (3H, s), 3.89 (2H, s), 3.85 (3H, s), 3.70-3.80 (1H, m), 3.49-3.60 (2H, m), 2.63 (1H, dd, J=5.6 Hz, J=13.7 Hz), 2.50 (1H, dd, J=7.1 Hz, J=13.4 Hz)

Mass spectrometric value (ESI-MS) 522, 523 (M−1)

Compound 1022 3-{[(2-Diethylamino-ethyl)-methyl-amino]-methyl}-N-[2-(3-fluoro-benzylidene-hydrazinocarbonyl)-4-methoxy-phenyl]-benzamide

The title compound 1022 was produced in substantially the same manner as in Example R.

¹H-NMR (CD₃OD, 400 MHz): δ 8.42 (1H, d, J=9.0 Hz), 8.36 (1H, s), 7.14-8.00 (10H, m), 3.90 (3H, s), 3.73 (2H, s), 3.25 (2H, t, J=6.0 Hz), 3.11 (4H, q, J=7.2 Hz), 2.75 (2H, t, J=5.9 Hz), 2.35 (3H, s), 1.23 (6H, t, J=7.3 Hz)

Mass spectrometric value (ESI-MS) 532, 533, 534 (M−1)

Compound 1023 N-[2-(4-Chloro-3-trifluoromethyl-benzylidene-hydrazinocarbonyl)-4-methoxy-phenyl]-3-{[(2-diethylamino-ethyl)-methyl-amino]-methyl}-benzamide

The title compound 1023 was produced in substantially the same manner as in Example R.

¹H-NMR (CD₃OD, 400 MHz): δ 8.36-8.42 (2H, m), 8.33 (1H, s), 8.03 (1H, d, J=8.5 Hz), 7.96 (1H, s), 7.89 (1H, d, J=7.8 Hz), 7.69 (1H, d, J=8.3 Hz), 7.59 (1H, d, J=7.8 Hz), 7.51 (1H, dd, J=7/Hz, J=7.7 Hz), 7.42 (1H, d, J=2.9 Hz), 7.22 (1H, dd, J=2.9 Hz, J=9.0 Hz), 3.90 (3H, s), 3.66 (2H, s), 2.70-2.77 (2H, m), 2.53-2.65 (6H, m), 2.28 (3H, s), 1.03 (6H, t, J=7.2 Hz)

Mass spectrometric value (ESI-MS) 616, 618, 619 (M−1)

Compound 1024 3-{[(2-Diethylamino-ethyl)-methyl-amino]-methyl}-N-[4-methoxy-2-(4-methoxy-benzylidene-hydrazinocarbonyl)-phenyl]-benzamide

The title compound 1024 was produced in substantially the same manner as in Example R.

¹H-NMR (CD₃OD, 400 MHz): δ 8.43 (1H, d, J=9.3 Hz), 8.30 (1H, s), 7.97 (1H, bs), 7.90 (1H, d, J=8.6 Hz), 7.78 (2H, d, J=8.8 Hz), 7.58 (1H, d, J=7.8 Hz), 7.52 (1H, dd, J=7.6 Hz, J=7.6 Hz), 7.40 (1H, d, J=2.9 Hz), 7.20 (1H, dd, J=2.9 Hz, J=9.2 Hz), 6.99 (2H, d, J=8.8 Hz), 3.89 (3H, s), 3.84 (3H, s), 3.68 (2H, s), 2.85-2.92 (2H, m), 2.75 (4H, q, J=7.1 Hz), 2.62 (2H, t, J=7.0 Hz), 2.30 (3H, s), 1.08 (6H, t, J=7.2 Hz)

Mass spectrometric value (ESI-MS) 544, 545, 546 (M−1)

Example S Compound 1025 3-{[(2-Diethylamino-ethyl)-methyl-amino]-methyl}-N-[2-(3-fluoro-benzylidene-hydrazinocarbonyl)-4-(2-methoxy-ethoxy)-phenyl]-benzamide

5-Hydroxy-2-nitro-benzoic acid (compound A′) (1.5 g) was dissolved in methanol (15 ml). Thionyl chloride (1.5 ml) was added dropwise to the solution on an ice bath, and the mixture was then stirred at 80° C. for 12 hr. After the completion of the reaction, the reaction solution was neutralized with a saturated aqueous sodium hydrogencarbonate solution, and was then subjected to separatory extraction with ethyl acetate. The organic layer was washed with saturated brine, was dried over sodium sulfate, and was then concentrated under the reduced pressure to give crude 5-hydroxy-2-nitro-benzoic acid methyl ester (1.1 g, crude yield 70%).

Crude 5-hydroxy-2-nitro-benzoic acid methyl ester (1.1 g) produced by the above process was dissolved in acetone (12 ml). Potassium carbonate (1.5 g) and 1-bromo-2-methoxyethane (compound D) (1.5 ml) were added to the solution at room temperature, and the mixture was then stirred at 70° C. for 20 hr. After the completion of the reaction, the reaction system was concentrated under the reduced pressure. Distilled water was then added to the residue, and the mixture was then subjected to separatory extraction with ethyl acetate. The organic layer was washed with saturated brine, was dried over sodium sulfate, and was then concentrated under the reduced pressure. The residue was purified by column chromatography eluted with a hexane-acetone system to give 5-methoxy-ethoxy-2-nitro-benzoic acid methyl ester (1.0 g, yield 73%).

Subsequently, 5-methoxy-ethoxy-2-nitro-benzoic acid methyl ester (1.0 g) produced by the above process was dissolved in methanol (10 ml), and platinum oxide (90 mg) was added to the solution at room temperature. The air in the reaction system was replaced by hydrogen, and the mixture was then stirred at that temperature for 5 hr. After the completion of the reaction, the atmosphere in the reaction system was replaced by nitrogen, and the reaction solution was filtered through Celite to remove platinum oxide. The filtrate was then concentrated under the reduced pressure, and the residue was purified by column chromatography eluted with a hexane-ethyl acetate system to give 2-amino-5-methoxy-ethoxybenzoic acid methyl ester (compound A) as a useful intermediate (770 mg, yield 83%)

2-Amino-5-methoxy-ethoxybenzoic acid methyl ester (compound A) (770 mg) produced by the above process was dissolved in anhydrous methylene chloride (10 ml). Pyridine (500 μl) and 3-(chloromethyl)benzoyl chloride (compound B) (600 μl) were added dropwise to the solution at 0° C., and the mixture was then stirred at room temperature for 3 hr. After the completion of the reaction, distilled water was added thereto at room temperature, and the mixture was then subjected to separatory extraction with chloroform. The organic layer was washed with saturated brine, was dried over sodium sulfate, and was then concentrated under the reduced pressure to precipitate crystals. The crude crystals were collected by Kiriyama Rohto and was washed with ether to give 2-(3-chloromethylbenzoylamino)-5-methoxy-ethoxybenzoic acid methyl ester (1.1 g, yield 89%).

Subsequently, 2-(3-chloromethylbenzoylamino)-5-methoxy-ethoxybenzoic acid methyl ester (1.1 g) produced by the above process was dissolved in anhydrous methylene chloride (15 ml). Triethylamine (1 ml) and N,N-diethyl-N′-methyl-ethylenediamine (compound B′) (900 μl) were added dropwise to the solution at room temperature, and the mixture was then stirred at that temperature for 12 hr. After the completion of the reaction, the reaction system was concentrated under the reduced pressure, and the residue was purified by column chromatography eluted with a chloroform-methanol system to give 2-(3-{[(2-diethylaminoethyl)-methylamino]-methyl}-benzoylamino)-5-(2-methoxy-ethoxy)-benzoic acid methyl ester as a useful intermediate (1.4 g, yield 100%).

2-(3-{[(2-Diethylamino-ethyl)-methylamino]-methyl}-benzoylamino)-5-(2-methoxy-ethoxy)-benzoic acid methyl ester (1.4 g) produced by the above process was dissolved in ethanol (15 ml). Hydrazine monohydrate (1.5 ml) was added dropwise to the solution at room temperature, and the mixture was then stirred at that temperature for 12 hr. After the completion of the reaction, the reaction system was concentrated under the reduced pressure, and the residue was purified by column chromatography eluted with a chloroform-methanol system to give 3-{[(2-dimethoxyamino-ethyl)-methyl-amino]-methyl}-N-[2-hydrazinocarbonyl-4-(2-methoxy-ethoxy)-phenyl]-benzamide (1.3 g, yield 89%).

Subsequently, 3-{[(2-dimethoxyamino-ethyl)-methyl-amino]-methyl}-N-[2-hydrazinocarbonyl-4-(2-methoxy-ethoxy)-phenyl]-benzamide (52 mg) produced by the above process was dissolved in anhydrous toluene (1 ml). 3-Fluorobenzaldehyde (compound C) (50 W) was added dropwise to the solution at room temperature, and the mixture was then stirred at 40° C. for 3 hr. After the completion of the reaction, the reaction solution was allowed to cool at room temperature and was then purified by column chromatography eluted with a chloroform-methanol system to give the title compound 1025 (50 mg, yield 78%).

¹H-NMR (CD₃OD, 400 MHz): δ 8.43 (1H, d, J=9.0 Hz), 8.36 (1H, s), 7.99 (1H, s), 7.90-7.95 (1H, m), 7.68-7.76 (2H, m), 7.08-7.64 (6H, m), 4.20-4.25 (2H, m), 3.77-3.82 (2H, m), 3.73 (2H, s), 3.45 (3H, s), 3.18 (2H, t, J=6.1 Hz), 3.04 (4H, q, J=7.2 Hz), 2.73 (2H, t, J=6.1 Hz), 2.34 (3H, s), 1.20 (6H, t, J=7.2 Hz)

Mass spectrometric value (ESI-MS) 576, 577, 578 (M−1)

Compound 1026 3-{[(2-Diethylamino-ethyl)-methyl-amino]-methyl}-N-[4-(2-methoxy-ethoxy)-2-(4-methyl-benzylidene-hydrazinocarbonyl)-phenyl]-benzamide

The title compound 1026 was produced in substantially the same manner as in Example S.

¹H-NMR (CD₃OD, 400 MHz): δ 8.43 (1H, d, J=9.0 Hz), 8.32 (1H, s), 7.97 (1H, s), 7.89-7.94 (1H, m), 7.73 (2H, d, J=8.0 Hz), 7.59 (1H, d, J=7.3 Hz), 7.52 (1H, dd, J=7.6 Hz, J=7.6 Hz), 7.43 (1H, d, J=2.9 Hz), 7.21-7.30 (3H, m), 4.20-4.25 (2H, m), 3.76-3.81 (2H, m), 3.68 (2H, s), 3.45 (3H, s), 2.58-2.90 (8H, m), 2.38 (3H, s), 2.30 (3H, s), 1.07 (6H, t, J=7.2 Hz)

Mass spectrometric value (ESI-MS) 572, 573, 574 (M−1)

Compound 1027 N-[2-(4-Chloro-3-trifluoromethyl-benzylidene-hydrazinocarbonyl)-4-(2-methoxy-ethoxy)-phenyl]-3-{[(2-diethylamino-ethyl)-methyl-amino]-methyl}-benzamide

The title compound 1027 was produced in substantially the same manner as in Example S.

¹H-NMR (CD₃OD, 400 MHz): δ 8.41 (1H, d, J=9.3 Hz), 8.38 (1H, s), 8.33 (1H, s), 8.03 (1H, d, J=8.3 Hz), 7.96 (1H, s), 7.88-7.92 (1H, m), 7.68 (1H, d, J=8.3 Hz), 7.59 (1H, d, J=7.8 Hz), 7.52 (1H, dd, J=7.6 Hz, J=7.6 Hz), 7.44 (1H, d, J=2.9 Hz), 7.24 (1H, dd, J=2.9 Hz, J=9.0 Hz), 4.20-4.25 (2H, m), 3.76-3.80 (2H, m), 3.67 (2H, s), 3.44 (3H, s), 2.81 (2H, t, J=6.8 Hz), 2.68 (4H, q, J=7.2 Hz), 2.59 (2H, t, J=7.1 Hz), 2.29 (3H, s), 1.06 (6H, t, J=7.3 Hz)

Mass spectrometric value (ESI-MS) 660, 662, 663 (M−1) 684 (M+23)

Compound 1028 3-{[(2-Diethylamino-ethyl)-methyl-amino]-methyl}-N-[2-(3-fluoro-benzylidene-hydrazinocarbonyl)-4,5-bis-(2-methoxy-ethoxy)-phenyl]-benzamide

The title compound 1028 was produced in substantially the same manner as in Example Q.

¹H-NMR (CD₃OD, 400 MHz): δ 8.49 (1H, bs), 8.37 (1H, bs), 8.00 (1H, bs), 7.95 (1H, d, J=7.3 Hz), 7.85-7.90 (1H, m), 7.40-7.76 (5H, m), 7.12-7.24 (1H, m), 4.22-4.32 (4H, m), 3.76-3.86 (4H, m), 3.72 (2H, s), 3.46 (3H, s), 3.46 (3H, s), 3.00-3.08 (2H, m), 2.82-2.96 (4H, m), 2.65-2.73 (2H, m), 2.33 (3H, s), 1.12-1.20 (6H, m)

Mass spectrometric value (ESI-MS) 650, 651, 652 (M−1) 672, 675 (M+23)

Compound 1029 N-[4,5-Bis-(2-methoxy-ethoxy)-2-(4-methyl-benzylidene-hydrazinocarbonyl)-phenyl]-3-{[(2-diethylamino-ethyl)-methyl-amino]-methyl}-benzamide

The title compound 1029 was produced in substantially the same manner as in Example Q.

¹H-NMR (CD₃OD, 400 MHz): δ 8.49 (1H, s), 8.34 (1H, s), 8.00 (1H, s), 7.92-7.98 (1H, m), 7.74 (2H, d, J=8.0 Hz), 7.51-7.65 (3H, m), 7.27 (2H, d, J=8.3 Hz), 4.23-4.33 (4H, m), 3.77-3.87 (4H, m), 3.71 (2H, s), 3.46 (3H, s), 3.46 (3H, s), 2.60-3.00 (8H, m), 2.39 (3H, s), 2.32 (3H, s), 1.10 (6H, t, J=7.2 Hz)

Mass spectrometric value (ESI-MS) 646, 647, 648 (M−1)

Compound 1030 3-{[(2-Diethylamino-ethyl)-methyl-amino]-methyl}-N-[2-(3,4-dimethyl-benzylidene-hydrazinocarbonyl)-4,5-bis-(2-methoxy-ethoxy)-phenyl]-benzamide

The title compound 1030 was produced in substantially the same manner as in Example Q.

¹H-NMR (CD₃OD, 400 MHz): δ 8.48 (1H, s), 8.31 (1H, s), 8.01 (1H, s), 7.95 (1H, d, J=7.3 Hz), 7.40-7.70 (5H, m), 7.18-7.23 (1H, m), 4.23-4.32 (4H, m), 3.76-3.86 (4H, m), 3.72 (2H, s), 3.45-3.80 (6H, m), 2.95-3.05 (2H, m), 2.80-2.90 (4H, m), 2.67 (2H, t, J=6.7 Hz), 2.26-2.34 (9H, m), 1.12 (6H, t, J=7.3 Hz)

Mass spectrometric value (ESI-MS) 660, 661, 662 (M−1)

Compound 1031 N-[2-(4-Chloro-3-trifluoromethyl-benzylidene-hydrazinocarbonyl)-4,5-bis-(2-methoxy-ethoxy)-phenyl]-3-{[(2-diethylamino-ethyl)-methyl-amino]-methyl}-benzamide

The title compound 1031 was produced in substantially the same manner as in Example Q.

¹H-NMR (CD₃OD, 400 MHz): δ 7.40-8.50 (10H, m), 4.23-4.33 (4H, m), 3.77-3.88 (4H, m), 3.74 (2H, s), 3.45-3.48 (6H, m), 2.65-3.30 (8H, m), 2.35 (3H, s), 1.21 (6H, t, J=7.2 Hz)

Mass spectrometric value (ESI-MS) 734, 736, 737 (M−1)

Compound 1032 3-{[(2-Diethylamino-ethyl)-methyl-amino]-methyl}-N-[2-(4-methoxy-benzylidene-hydrazinocarbonyl)-4,5-bis-(2-methoxy-ethoxy)-phenyl]-benzamide

The title compound 1032 was produced in substantially the same manner as in Example Q.

¹H-NMR (CD₃OD, 400 MHz): δ 8.48 (1H, s), 8.32 (1H, s), 8.01 (1H, s), 7.95 (1H, d, J=7.3 Hz), 7.79 (2H, d, J=8.8 Hz), 7.50-7.70 (3H, m), 7.00 (2H, d, J=8.8 Hz), 4.23-4.33 (4H, m), 3.76-3.88 (7H, m), 3.72 (2H, s), 3.45-3.48 (6H, m), 3.05-3.10 (2H, m), 2.90-3.00 (4H, m), 2.65-2.73 (2H, m), 2.33 (3H, s), 1.16 (6H, t, J=7.2 Hz)

Mass spectrometric value (ESI-MS) 662, 663, 664 (M−1)

Compound 1033 3-{[(2-Diethylamino-ethyl)-methyl-amino]-methyl}-N-{2-(3-fluoro-benzylidene-hydrazinocarbonyl)-4-[2-(2-methoxy-ethoxy)-ethoxy]-phenyl}-benzamide

The title compound 1033 was produced in substantially the same manner as in Example S.

¹H-NMR (CDCL₃, 400 MHz): δ 11.36 (1H, bs), 8.48 (1H, bs), 8.21 (1H, s), 7.65-7.93 (6H, m), 7.10-7.38 (5H, m), 4.12 (2H, bs), 3.78 (2H, bs), 3.63-3.67 (4H, m), 3.56-3.62 (2H, m), 3.50-3.55 (2H, m), 3.28 (3H, s), 3.05 (4H, bs), 2.75-2.80 (2H, m), 2.20-2.40 (3H, m), 1.15-1.25 (6H, m)

Mass spectrometric value (ESI-MS) 620, 621, 622 (M−1)

Compound 1034 3-{[(2-Diethylamino-ethyl)-methyl-amino]-methyl}-N-[4-[2-(2-methoxy-ethoxy)-ethoxy]-2-(4-methyl-benzylidene-hydrazinocarbonyl)-phenyl]-benzamide

The title compound 1034 was produced in substantially the same manner as in Example S.

¹H-NMR (CDCL₃, 400 MHz): δ 11.37 (1H, bs), 8.49 (1H, d, J=9.0 Hz), 8.20 (1H, s), 7.84-7.90 (2H, m), 7.80 (1H, d, J=7.6 Hz), 7.60 (2H, d, J=7.8 Hz), 7.20-7.46 (3H, m), 6.98-7.20 (3H, m), 4.05-4.10 (2H, m), 3.68-3.74 (2H, m), 3.61-3.65 (2H, m), 3.50-3.55 (4H, m), 3.28 (3H, s), 2.50-2.70 (8H, m), 2.30 (3H, s), 2.17 (3H, s), 0.95-1.04 (6H, m)

Mass spectrometric value (ESI-MS) 616, 617, 618 (M−1)

Compound 1035 3-{[(2-Diethylamino-ethyl)-methyl-amino]-methyl}-N-{2-(3,4-dimethyl-benzylidene-hydrazinocarbonyl)-4-[2-(2-methoxy-ethoxy)-ethoxy]-phenyl}-benzamide

The title compound 1035 was produced in substantially the same manner as in Example S.

¹H-NMR (CDCL₃, 400 MHz): δ 11.37 (1H, bs), 8.48 (1H, d, J=9.0 Hz), 8.19 (1H, s), 7.86 (1H, s), 7.80 (1H, d, J=7.6 Hz), 7.54 (1H, s), 7.20-7.46 (4H, m), 6.96-7.12 (3H, m), 4.03-4.10 (2H, m), 3.69 (2H, bs), 3.60-3.65 (2H, m), 3.50-3.55 (4H, m), 3.27 (3H, s), 2.47-2.70 (8H, m), 2.21 (6H, s), 2.16 (3H, s), 0.98 (6H, t, J=7.0 Hz)

Mass spectrometric value (ESI-MS) 630, 631, 632 (M−1)

Compound 1036 N-{2-(4-Chloro-3-trifluoromethyl-benzylidene-hydrazinocarbonyl)-4-[2-(2-methoxy-ethoxy)-ethoxy]-phenyl}-3-{[(2-diethylamino-ethyl)-methyl-amino]-methyl}-benzamide

The title compound 1036 was produced in substantially the same manner as in Example S.

¹H-NMR (CD₃OD, 400 MHz): δ 8.41 (1H, d, J=9.0 Hz), 8.38 (1H, s), 8.32 (1H, s), 8.03 (1H, d, J=8.3 Hz), 7.96 (1H, s), 7.87-7.92 (1H, m), 7.68 (1H, d, J=8.3 Hz), 7.59 (1H, d, J=7.8 Hz), 7.44-7.54 (2H, m), 7.24 (1H, dd, J=2.9 Hz, J=9.0 Hz), 4.20-4.26 (2H, m), 3.84-3.90 (2H, m), 3.68-3.74 (2H, m), 3.66 (2H, s), 3.55-3.60 (2H, m), 3.37 (3H, s), 2.53-2.75 (8H, m), 2.28 (3H, s), 1.03 (6H, t, J=7.2 Hz)

Mass spectrometric value (ESI-MS) 704, 706, 707 (M−1)

Compound 1037 3-{[(2-Diethylamino-ethyl)-methyl-amino]-methyl}-N-{2-(4-methoxy-benzylidene-hydrazinocarbonyl)-4-[2-(2-methoxy-ethoxy)-ethoxy]-phenyl}-benzamide

The title compound 1037 was produced in substantially the same manner as in Example S.

¹H-NMR (CD₃OD, 400 MHz): δ 8.44 (1H, d, J=9.3 Hz), 8.29 (1H, s), 7.96 (1H, bs), 7.87-7.92 (1H, m), 7.78 (2H, d, J=8.8 Hz), 7.58 (1H, d, J=7.6 Hz), 7.51 (1H, dd, J=7.6 Hz, J=7.6 Hz), 7.43 (1H, d, J=2.9 Hz), 7.22 (1H, dd, J=2.9 Hz, J=9.0 Hz), 6.99 (2H, d, J=9.0 Hz), 4.21-4.25 (2H, m), 3.85-3.88 (2H, m), 3.84 (3H, s), 3.69-3.72 (2H, m), 3.67 (2H, s), 3.56-3.59 (2H, m), 3.37 (3H, s), 2.55-2.80 (8H, m), 2.28 (3H, s), 1.04 (6H, t, J=7.2 Hz)

Mass spectrometric value (ESI-MS) 632, 633, 634 (M−1)

Example T Compound 1038 N-[2-(4-Chloro-3-trifluoromethyl-benzylidene-hydrazinocarbonyl)-4-(3-piperidin-1-yl-propoxy)-phenyl]-3-{[(2-diethylamino-ethyl)-methyl-amino]-methyl}-benzamide

5-Hydroxy-2-nitro-benzoic acid (compound A′) (2.0 g) was dissolved in methanol (30 ml). Thionyl chloride (3.0 ml) was added dropwise to the solution on an ice bath, and the mixture was then stirred at 75° C. for 96 hr. After the completion of the reaction, the reaction solution was neutralized with a saturated aqueous sodium hydrogencarbonate solution and was then subjected to separatory extraction with ethyl acetate. The organic layer was washed with saturated brine, was dried over sodium sulfate, and was then concentrated under the reduced pressure to give crude 5-hydroxy-2-nitro-benzoic acid methyl ester (2.2 g, crude yield 100%).

Subsequently, crude 5-hydroxy-2-nitro-benzoic acid methyl ester (2.2 g) produced by the above process was dissolved in acetone (15 ml). Potassium carbonate (3.0 g) and 1-bromo-3-chloro-propane (compound D) (3.1 ml) were added to the solution at room temperature, and the mixture was then stirred at that temperature for 2 hr. After the completion of the reaction, the reaction system was concentrated under the reduced pressure. Distilled water was then added to the residue, the mixture was subjected to separatory extraction with chloroform, and the organic layer was washed with saturated brine, was dried over sodium sulfate, and was then concentrated under the reduced pressure. The residue was purified by column chromatography eluted with a hexane-acetone system to give 5-(3-chloro-propoxy)-2-nitro-benzoic acid methyl ester (2.9 g, yield 96%).

5-(3-Chloro-propoxy)-2-nitro-benzoic acid methyl ester (2.9 g) produced by the above process was dissolved in acetone (30 ml). Potassium carbonate (3.0 g) and piperidine (compound E) (2.0 ml) were added to the solution at room temperature, and the mixture was then stirred at 70° C. for 24 hr. After the completion of the reaction, the reaction system was concentrated under the reduced pressure. Distilled water was then added to the residue, the mixture was subjected to separatory extraction with chloroform, and the organic layer was washed with saturated brine, was dried over sodium sulfate, and was then concentrated under the reduced pressure. The residue was purified by column chromatography eluted with a chloroform-methanol system to give 2-nitro-5-(3-piperidin-1-yl-propoxy)-benzoic acid methyl ester (2.4 g, yield 69%).

Subsequently, 2-nitro-5-(3-piperidin-1-yl-propoxy)-benzoic acid methyl ester (2.4 g) produced by the above process was dissolved in methanol (24 ml), and platinum oxide (220 mg) was added to the solution at room temperature. The air in the reaction system was replaced by hydrogen, and the mixture was then stirred at that temperature for 12 hr. After the completion of the reaction, the atmosphere in the reaction system was replaced by nitrogen, and the reaction solution was filtered through Celite to remove platinum oxide. The filtrate was then concentrated under the reduced pressure, and the residue was purified by column chromatography eluted with a chloroform-methanol system to give 2-amino-5-(3-piperidin-1-yl-propoxy)-benzoic acid methyl ester (compound A) as a useful intermediate (1.1 g, yield 50%).

2-Amino-5-(3-piperidin-1-yl-propoxy)-benzoic acid methyl ester (compound A) (1.1 g) produced by the above process was dissolved in anhydrous methylene chloride (12 ml). Pyridine (600 μl) and 3-(chloromethyl)benzoyl chloride (compound B) (600 μl) were added dropwise to the solution at 0° C., and the mixture was stirred at room temperature for one hr. After the completion of the reaction, distilled water was added thereto at room temperature, and the mixture was then subjected to separatory extraction with chloroform. The organic layer was washed with saturated brine, was dried over sodium sulfate, and was then concentrated under the reduced pressure. The residue was purified by column chromatography eluted with a chloroform-methanol system to give 2-(3-chloromethyl-benzoylamino)-5-(3-piperidin-1-yl-propoxy)-benzoic acid methyl ester (1.5 g, yield 93%).

Subsequently, 2-(3-chloromethyl-benzoylamino)-5-(3-piperidin-1-yl-propoxy)-benzoic acid methyl ester (1.5 g) produced by the above process was dissolved in anhydrous methylene chloride (11 ml). Triethylamine (450 μl) and N,N-diethyl-N′-methyl-ethylenediamine (compound B′) (480 μl) was added dropwise to the solution at room temperature, and the mixture was then stirred at that temperature for 12 hr. After the completion of the reaction, the reaction system was concentrated under the reduced pressure, and the residue was purified by column chromatography eluted with a chloroform-methanol system to give 2-(3-{[(2-diethylamino-ethyl)-methyl-amino]-methyl}benzoylamino)-5-(3-piperidin-1-yl-propoxy)-benzoic acid methyl ester as a useful intermediate (290 mg, yield 34%).

2-(3-{[(2-Diethylamino-ethyl)-methyl-amino]-methyl}benzoyl-amino)-5-(3-piperidin-1-yl-propoxy)-benzoic acid methyl ester (290 mg) produced by the above process was dissolved in ethanol (4 ml). Hydrazine monohydrate (300 μl) was added dropwise to the solution at room temperature, and the mixture was then stirred at that temperature for 6 hr. After the completion of the reaction, the reaction system was concentrated under the reduced pressure, and the residue was purified by column chromatography eluted with a chloroform-methanol system to give 3-{[(2-diethylamino-ethyl)-methyl-amino]-methyl}-N-[2-hydrazinocarbonyl-4-(3-piperidin-1-yl-propoxy)-phenyl]-benzamide (140 mg, yield 49%).

Subsequently, 3-{[(2-diethylamino-ethyl)-methyl-amino]-methyl}-N-[2-hydrazinocarbonyl-4-(3-piperidin-1-yl-propoxy)-phenyl]-benzamide (50 mg) produced by the above process was dissolved in anhydrous toluene (1.2 ml). 4-Chloro-3-(trifluoromethyl)benzaldehyde (compound C) (50 μl) was added dropwise to the solution at room temperature, and the mixture was then stirred at that temperature for 12 hr. After the completion of the reaction, the reaction system was concentrated. The residue was purified by column chromatography eluted with a chloroform-methanol system to give the title compound 1038 (67 mg, yield 100%).

¹H-NMR (CD₃OD, 400 MHz): δ 8.40 (1H, d, J=9.0 Hz), 8.37 (1H, s), 8.32 (1H, s), 8.03 (1H, d, J=8.5 Hz), 7.95 (1H, s), 7.85-7.94 (1H, m), 7.68 (1H, d, J=8.3 Hz), 7.56-7.63 (1H, m), 7.51 (1H, dd, J=7.7 Hz, J=7.7 Hz), 7.44 (1H, d, J=2.7 Hz), 7.20 (1H, dd, J=2.7 Hz, J=9.0 Hz), 4.08-4.15 (2H, m), 3.62-3.70 (2H, m), 2.45-2.72 (14H, m), 2.27 (3H, s), 1.98-2.07 (2H, m), 1.60-1.70 (4H, m), 1.45-1.54 (2H, m), 1.01 (6H, t, J=7.2 Hz)

Mass spectrometric value (ESI-MS) 727, 728, 730 (M−1)

Compound 1039 N-[2-(4-Chloro-3-trifluoromethyl-benzylidene-hydrazinocarbonyl)-4-(3-piperidin-1-yl-propoxy)-phenyl]-3-(2-hydroxy-ethylsulfanylmethyl)-benzamide

The title compound 1039 was produced in substantially the same manner as in Example T.

¹H-NMR (CD₃OD, 400 MHz): δ 8.41 (1H, d, J=9.0 Hz), 8.37 (1H, s), 8.30-8.34 (1H, m), 8.04 (1H, d, J=7.1 Hz), 7.83-7.94 (2H, m), 7.68 (1H, d, J=8.3 Hz), 7.59 (1H, d, J=7.6 Hz), 7.50 (1H, dd, J=7.8 Hz, J=7.8 Hz), 7.42 (1H, d, J=2.7 Hz), 7.22 (1H, dd, J=2.7 Hz, J=9.2 Hz), 4.14 (2H, t, J=6.1 Hz), 3.86 (2H, s), 3.68 (2H, t, J=6.8 Hz), 2.65-2.80 (6H, m), 2.57 (2H, t, J=6.8 Hz), 2.05-2.15 (2H, m), 1.67-1.75 (4H, m), 1.50-1.60 (2H, m)

Mass spectrometric value (ESI-MS) 675, 677, 678 (M−1)

Compound 1040 3-(2-Hydroxy-ethylsulfanylmethyl)-N-[2-(4-methoxy-benzylidene-hydrazinocarbonyl)-4-(3-piperidin-1-yl-propoxy)-phenyl]-benzamide

The title compound 1040 was produced in substantially the same manner as in Example T.

¹H-NMR (CD₃OD, 400 MHz): δ 8.45 (1H, d, J=9.0 Hz), 8.28 (1H, s), 7.92 (1H, bs), 7.85 (1H, d, J=8.0 Hz), 7.78 (2H, d, J=8.3 Hz), 7.58 (1H, d, J=7.8 Hz), 7.49 (1H, dd, J=7.7 Hz, J=7.7 Hz), 7.39 (1H, d, J=2.4 Hz), 7.18 (1H, d, J=9.3 Hz), 6.98 (2H, d, J=8.3 Hz), 4.11 (2H, t, J=5.7 Hz), 3.86 (2H, s), 3.83 (3H, s), 3.68 (2H, t, J=6.8 Hz), 2.54-2.68 (8H, m), 2.00-2.09 (2H, m), 1.62-1.70 (4H, m), 1.47-1.57 (2H, m)

Mass spectrometric value (ESI-MS) 603, 604, 605 (M−1)

Compound 1041 N-[2-(3,4-Dimethyl-benzylidene-hydrazinocarbonyl)-4-(3-piperidin-1-yl-propoxy)-phenyl]-3-(2-hydroxy-ethylsulfanylmethyl)-benzamide

The title compound 1041 was produced in substantially the same manner as in Example T.

¹H-NMR (CD₃OD, 400 MHz): δ 8.45 (1H, d, J=9.3 Hz), 8.28 (1H, s), 7.93 (1H, bs), 7.86 (1H, d, J=7.8 Hz), 7.65 (1H, s), 7.59 (1H, d, J=7.8 Hz), 7.53 (1H, d, J=8.1 Hz), 7.49 (1H, dd, J=7.7 Hz, J=7.7 Hz), 7.41 (1H, d, J=2.7 Hz), 7.16-7.23 (2H, m), 4.13 (2H, t, J=6.1 Hz), 3.87 (2H, s), 3.68 (2H, t, J=6.8 Hz), 2.55-2.73 (8H, m), 2.31 (3H, s), 2.30 (3H, s), 2.00-2.10 (2H, m), 1.65-1.75 (4H, m), 1.50-1.58 (2H, m)

Mass spectrometric value (ESI-MS) 601, 602, 603 (M−1)

Compound 1042 3-(2-Hydroxy-ethylsulfanylmethyl)-N-[2-(4-methyl-benzylidene-hydrazinocarbonyl)-4-(2-piperidin-1-yl-ethoxy)-phenyl]-benzamide

The title compound 1042 was produced in substantially the same manner as in Example T.

¹H-NMR (CD₃OD, 400 MHz): δ 8.46 (1H, d, J=9.0 Hz), 8.32 (1H, s), 7.93 (1H, bs), 7.86 (1H, d, J=7.8 Hz), 7.73 (2H, d, J=8.3 Hz), 7.59 (1H, d, J=7.8 Hz), 7.49 (1H, dd, J=7.7 Hz, J=7.7 Hz), 7.42 (1H, d, J=2.9 Hz), 7.25 (2H, d, J=7.8 Hz), 7.22 (1H, dd, J=2.9 Hz, J=9.3 Hz), 4.23 (2H, t, J=5.6 Hz), 3.87 (2H, s), 3.68 (2H, t, J=6.8 Hz), 2.83 (2H, t, J=5.7 Hz), 2.55-2.65 (6H, m), 2.38 (3H, s), 1.62-1.70 (4H, m), 1.46-1.55 (2H, m)

Mass spectrometric value (ESI-MS) 573, 574, 575 (M−1)

Compound 1043 N-[2-(3,4-Dimethyl-benzylidene-hydrazinocarbonyl)-4-(2-piperidin-1-yl-ethoxy)-phenyl]-3-(2-hydroxy-ethylsulfanylmethyl)-benzamide

The title compound 1043 was produced in substantially the same manner as in Example T.

¹H-NMR (CD₃OD, 400 MHz): δ 8.46 (1H, d, J=9.0 Hz), 8.29 (1H, s), 7.93 (1H, s), 7.86 (1H, d, J=7.6 Hz), 7.66 (1H, s), 7.60 (1H, d, J=7.6 Hz), 7.54 (1H, d, J=8.0 Hz), 7.50 (1H, dd, J=7.7 Hz, J=7.7 Hz), 7.43 (1H, d, J=3.0 Hz), 7.17-7.25 (2H, m), 4.23 (2H, t, J=5.6 Hz), 3.87 (2H, s), 3.68 (2H, t, J=6.7 Hz), 2.83 (2H, t, J=5.5 Hz), 2.55-2.65 (6H, m), 2.32 (3H, s), 2.30 (3H, s), 1.61-1.70 (4H, m), 1.45-1.55 (2H, m)

Mass spectrometric value (ESI-MS) 587, 588 (M−1)

Compound 1044 N-[2-(4-Chloro-3-trifluoromethyl-benzylidene-hydrazinocarbonyl)-4-(2-piperidin-1-yl-ethoxy)-phenyl]-3-(2-hydroxy-ethylsulfanylmethyl)-benzamide

The title compound 1044 was produced in substantially the same manner as in Example T.

¹H-NMR (CD₃OD, 400 MHz): δ 8.44 (1H, d, J=9.0 Hz), 8.38 (1H, s), 8.34 (1H, bs), 8.03-8.08 (1H, m), 7.93 (1H, bs), 7.86 (1H, d, J=7.8 Hz), 7.69 (1H, d, J=8.3 Hz), 7.60 (1H, d, J=8.6 Hz), 7.50 (1H, dd, J=7.8 Hz, J=7.8 Hz), 7.44 (1H, d, J=2.7 Hz), 7.24 (1H, dd, J=2.9 Hz, J=9.3 Hz), 4.23 (2H, t, J=5.6 Hz), 3.86 (2H, s), 3.68 (2H, t, J=7.0 Hz), 2.83 (2H, t, J=5.6 Hz), 2.55-2.63 (6H, m), 1.62-1.70 (4H, m), 1.45-1.55 (2H, m)

Mass spectrometric value (ESI-MS) 661, 663, 664 (M−1)

Compound 1045 3-(2-Hydroxy-ethylsulfanylmethyl)-N-[2-(4-methoxy-benzylidene-hydrazinocarbonyl)-4-(2-piperidin-1-yl-ethoxy)-phenyl]-benzamide

The title compound 1045 was produced in substantially the same manner as in Example T.

¹H-NMR (CD₃OD, 400 MHz): δ 8.47 (1H, d, J=9.3 Hz), 8.30 (1H, s), 7.93 (1H, bs), 7.86 (1H, d, J=8.1 Hz), 7.80 (2H, d, J=8.8 Hz), 7.60 (1H, d, J=7.8 Hz), 7.50 (1H, dd, J=7.7 Hz, J=7.7 Hz), 7.42 (1H, d, J=2.9 Hz), 7.22 (1H, dd, J=2.9 Hz, J=9.0 Hz), 6.99 (2H, d, J=8.8 Hz), 4.23 (2H, t, J=5.6 Hz), 3.87 (2H, s), 3.84 (3H, s), 3.68 (2H, t, J=6.8 Hz), 2.82 (2H, t, J=5.6 Hz), 2.55-2.63 (6H, m), 1.62-1.70 (4H, m), 1.45-1.55 (2H, m)

Mass spectrometric value (ESI-MS) 589, 590 (M−1)

Compound 1046 N-[4-Cyclohexylmethoxy-2-(3-fluoro-benzylidene-hydrazinocarbonyl)-phenyl]-3-{[(2-diethylamino-ethyl)-methyl-amino]-methyl}-benzamide

The title compound 1046 was produced in substantially the same manner as in Example S.

¹H-NMR (CD₃OD, 400 MHz): δ 8.41 (1H, d, J=9.0 Hz), 8.34 (1H, s), 7.97 (1H, s), 7.88-7.93 (1H, m), 7.68-7.78 (1H, m), 7.30-7.64 (5H, m), 7.08-7.22 (2H, m), 3.88 (2H, d, J=6.1 Hz), 3.69 (2H, s), 2.80-2.93 (2H, m), 2.68-2.80 (4H, m), 2.55-2.65 (2H, m), 2.30 (3H, s), 1.68-1.95 (5H, m), 1.10-1.42 (6H, m), 1.08 (6H, t, J=7.2 Hz)

Mass spectrometric value (ESI-MS) 614, 615, 616 (M−1) 638 (M+23)

Compound 1047 N-[4-Cyclohexylmethoxy-2-(4-methyl-benzylidene-hydrazinocarbonyl)-phenyl]-3-{[(2-diethylamino-ethyl)-methyl-amino]-methyl}-benzamide

The title compound 1047 was produced in substantially the same manner as in Example S.

¹H-NMR (CD₃OD, 400 MHz): δ 8.41 (1H, d, J=9.0 Hz), 8.32 (1H, s), 7.96 (1H, bs), 7.88-7.92 (1H, m), 7.73 (2H, d, J=8.0 Hz), 7.58 (1H, d, J=7.6 Hz), 7.52 (1H, dd, J=7.6 Hz, J=7.6 Hz), 7.39 (1H, d, J=2.8 Hz), 7.26 (2H, d, J=8.1 Hz), 7.19 (1H, dd, J=2.9 Hz, J=9.0 Hz), 3.88 (2H, d, J=6.4 Hz), 3.68 (2H, s), 2.55-2.85 (8H, m), 2.38 (3H, s), 2.29 (3H, s), 1.70-1.95 (5H, m), 1.10-1.42 (6H, m), 1.05 (6H, t, J=7.2 Hz)

Mass spectrometric value (ESI-MS) 610, 611, 612 (M−1)

Compound 1048 N-[4-Cyclohexylmethoxy-2-(3,4-dimethyl-benzylidene-hydrazinocarbonyl)-phenyl]-3-{[(2-diethylamino-ethyl)-methyl-amino]-methyl}-benzamide

The title compound 1048 was produced in substantially the same manner as in Example S.

¹H-NMR (CD₃OD, 400 MHz): δ 8.42 (1H, d, J=9.3 Hz), 8.28 (1H, s), 7.96 (1H, bs), 7.88-7.93 (1H, m), 7.64 (1H, s), 7.58 (1H, d, J=7.6 Hz), 7.49-7.55 (2H, m), 7.39 (1H, d, J=2.9 Hz), 7.16-7.23 (2H, m), 3.87 (2H, d, J=6.4 Hz), 3.67 (2H, s), 2.55-2.80 (8H, m), 2.31 (3H, s), 2.30 (3H, s), 2.29 (3H, s), 1.70-1.95 (5H, m), 1.10-1.42 (6H, m), 1.04 (6H, t, J=7.2 Hz)

Mass spectrometric value (ESI-MS) 624, 625, 626 (M−1) 670, 671-(M+23×2)

Compound 1049 N-[2-(4-Chloro-3-trifluoromethyl-benzylidene-hydrazinocarbonyl)-4-cyclohexylmethoxy-phenyl]-3-{[(2-diethylamino-ethyl)-methyl-amino]-methyl}-benzamide

The title compound 1049 was produced in substantially the same manner as in Example S.

¹H-NMR (CD₃OD, 400 MHz): δ 8.30-8.42 (2H, m), 8.03 (1H, d, J=8.3 Hz), 7.96 (1H, s), 7.87-7.92 (1H, m), 7.69 (1H, d, J=8.6 Hz), 7.59 (1H, d, J=7.6 Hz), 7.48-7.54 (2H, m), 7.41 (1H, d, J=2.7 Hz), 7.20 (1H, dd, J=2.7 Hz, J=9.0 Hz), 3.88 (2H, d, J=6.3 Hz), 3.67 (2H, s), 2.54-2.78 (8H, m), 2.28 (3H, s), 1.70-1.95 (5H, m), 1.08-1.42 (6H, m), 1.04 (6H, t, J=7.2 Hz)

Mass spectrometric value (ESI-MS) 698, 700, 701 (M−1)

Compound 1050 N-[4-Cyclohexylmethoxy-2-(4-methoxy-benzylidene-hydrazinocarbonyl)-phenyl]-3-{[(2-diethylamino-ethyl)-methyl-amino]-methyl}-benzamide

The title compound 1050 was produced in substantially the same manner as in Example S.

¹H-NMR (CD₃OD, 400 MHz): δ 8.42 (1H, d, J=9.0 Hz), 8.29 (1H, s), 7.96 (1H, bs), 7.87-7.93 (1H, m), 7.78 (2H, d, J=8.8 Hz), 7.59 (1H, d, J=7.3 Hz), 7.51 (1H, dd, J=7.7 Hz, J=7.7 Hz), 7.38 (1H, d, J=3.0 Hz), 7.18 (1H, dd, J=3.0 Hz, J=9.3 Hz), 6.99 (2H, d, J=8.8 Hz), 3.87 (2H, d, J=6.4 Hz), 3.84 (3H, s), 3.67 (2H, s), 2.54-2.80 (8H, m), 2.28 (3H, s), 1.70-1.95 (5H, m), 1.10-1.42 (6H, m), 1.03 (6H, t, J=7.2 Hz)

Mass spectrometric value (ESI-MS) 626, 627, 628 (M−1) 650 (M+23)

Compound 1051 N-[2-(3-Fluoro-benzylidene-hydrazinocarbonyl)-4-(4-fluoro-butoxy)-phenyl]-3-(2-hydroxy-ethylsulfanylmethyl)-benzamide

The title compound 1051 was produced in substantially the same manner as in Example S.

¹H-NMR (CD₃OD, 400 MHz): δ 8.43 (1H, d, J=9.0 Hz), 8.34 (1H, s), 7.93 (1H, s), 7.86 (1H, d, J=7.8 Hz), 7.70 (1H, d, J=9.0 Hz), 7.59 (2H, d, J=7.6 Hz), 7.40-7.52 (3H, m), 7.13-7.25 (2H, m), 4.55-4.60 (1H, m), 4.46 (1H, t, J=5.7 Hz), 4.13 (2H, t, J=5.9 Hz), 3.87 (2H, s), 3.68 (2H, t, J=6.8 Hz), 2.58 (2H, t, J=6.8 Hz), 1.80-1.95 (4H, m)

Mass spectrometric value (ESI-MS) 540, 541 (M−1) 564 (M+23)

Compound 1052 N-[4-(4-Fluoro-butoxy)-2-(4-methyl-benzylidene-1-hydrazinocarbonyl)-phenyl]-3-(2-hydroxy-ethylsulfanylmethyl)-benzamide

The title compound 1052 was produced in substantially the same manner as in Example S.

¹H-NMR (CD₃OD, 400 MHz): δ 8.45 (1H, d, J=9.0 Hz), 8.31 (1H, s), 7.93 (1H, bs), 7.86 (1H, d, J=8.0 Hz), 7.73 (2H, d, J=8.0 Hz), 7.59 (1H, d, J=8.1 Hz), 7.49 (1H, dd, J=7.6 Hz, J=7.6 Hz), 7.42 (1H, d, J=2.9 Hz), 7.26 (2H, d, J=7.8 Hz), 7.21 (1H, dd, J=2.9 Hz, J=9.3 Hz), 4.55-4.60 (1H, m), 4.46 (1H, t, J=5.7 Hz), 4.13 (2H, t, J=6.0 Hz), 3.87 (2H, s), 3.68 (2H, t, J=6.8 Hz), 2.57 (2H, t, J=6.8 Hz), 2.38 (3H, s), 1.80-1.96 (4H, m)

Mass spectrometric value (ESI-MS) 536, 537 (M−1)

Compound 1053 N-[2-(3,4-Dimethyl-benzylidene-hydrazinocarbonyl)-4-(4-fluoro-butoxy)-phenyl]-3-(2-hydroxy-ethylsulfanylmethyl)-benzamide

The title compound 1053 was produced in substantially the same manner as in Example S.

¹H-NMR (CD₃OD, 400 MHz): δ 8.45 (1H, d, J=9.3 Hz), 8.28 (1H, s), 7.93 (1H, s), 7.86 (1H, d, J=8.0 Hz), 7.65 (1H, s), 7.59 (1H, d, J=7.6 Hz), 7.53 (1H, d, J=8.8 Hz), 7.49 (1H, dd, J=7.7 Hz, J=7.7 Hz), 7.41 (1H, d, J=2.7 Hz), 7.17-7.24 (2H, m), 4.55-4.60 (1H, m), 4.46 (1H, t, J=5.7 Hz), 4.12 (2H, t, J=6.0 Hz), 3.87 (2H, s), 3.68 (2H, t, J=6.8 Hz), 2.57 (2H, t, J=6.8 Hz), 2.31 (3H, s), 2.30 (3H, s), 1.83-1.95 (4H, m)

Mass spectrometric value (ESI-MS) 550, 551 (M−1)

Compound 1054 N-[2-(4-Chloro-3-trifluoromethyl-benzylidene-hydrazinocarbonyl)-4-(4-fluoro-butoxy)-phenyl]-3-(2-hydroxy-ethylsulfanylmethyl)-benzamide

The title compound 1054 was produced in substantially the same manner as in Example S.

¹H-NMR (CD₃OD, 400 MHz): δ 8.42 (1H, d, J=9.2 Hz), 8.37 (1H, s), 8.32 (1H, s), 8.01-8.05 (1H, m), 7.92 (1H, s), 7.85 (1H, d, J=7.8 Hz), 7.67 (1H, d, J=8.3 Hz), 7.59 (1H, d, J=7.6 Hz), 7.49 (1H, dd, J=7.7 Hz, J=7.7 Hz), 7.42 (1H, d, J=2.7 Hz), 7.22 (1H, dd, J=2.7 Hz, J=9.2 Hz), 4.55-4.60 (1H, m), 4.46 (1H, t, J=5.7 Hz), 4.12 (2H, t, J=5.8 Hz), 3.86 (2H, s), 3.68 (2H, t, J=6.8 Hz), 2.57 (2H, t, J=7.0 Hz), 1.80-1.95 (4H, m)

Mass spectrometric value (ESI-MS) 624, 626, 627 (M−1)

Compound 1055 N-[4-(4-Fluoro-butoxy)-2-(4-methoxy-benzylidene-hydrazinocarbonyl)-phenyl]-3-(2-hydroxy-ethylsulfanylmethyl)-benzamide

The title compound 1055 was produced in substantially the same manner as in Example S.

¹H-NMR (CD₃OD, 400 MHz): δ 6.95-8.60 (12H, m), 4.55-4.62 (1H, m), 4.46 (1H, t, J=5.7 Hz), 4.12 (2H, t, J=6.0 Hz), 3.83-3.88 (3H, m), 3.79 (2H, s), 3.68 (2H, t, J=6.8 Hz), 2.57 (2H, t, J=6.8 Hz), 1.80-1.95 (4H, m)

Mass spectrometric value (ESI-MS) 552, 553 (M−1)

Compound 1056 3-{[Bis-(2-diethylamino-ethyl)-amino]-methyl}-N-[3-(4-methyl-benzylidene-hydrazinocarbonyl)-4,5,6,7-tetrahydro-benzo[b]thiophen-2-yl]-benzamide

The title compound 1056 was produced in substantially the same manner as in Example B.

¹H-NMR (CDCl₃, 400 MHz): δ 0.98 (12H, t, J=7.1 Hz), 1.92 (4H, m), 2.40 (3H, s), 2.45-2.65 (16H, m), 2.76 (2H, m), 2.89 (2H, m), 3.72 (2H, s), 7.24 (2H, m), 7.43 (1H, dd, J=7.7 Hz, J=7.7 Hz), 7.60 (1H, d, J=7.3 Hz), 7.69 (2H, d, J=8.0 Hz), 7.92 (1H, m), 8.00 (1H, s), 8.08 (1H, s)

Mass spectrometric value (ESI-MS) 644 (M−1)

Compound 1057 3-{[(2-Diethylamino-ethyl)-methyl-amino]-methyl}-N-[2-(3-fluoro-benzyl idene-hydrazinocarbonyl)-4-(4-fluoro-butoxy)-phenyl]-benzamide

The title compound 1057 was produced in substantially the same manner as in Example S.

¹H-NMR (CD₃OD, 400 MHz): δ 8.41 (1H, d, J=9.0 Hz), 8.34 (1H, s), 7.88-7.98 (2H, m), 7.40-7.78 (6H, m), 7.14-7.26 (2H, m), 4.55-4.60 (1H, m), 4.46 (1H, t, J=5.7 Hz), 4.13 (2H, t, J=5.9 Hz), 3.68 (2H, s), 2.81 (2H, t, J=6.8 Hz), 2.68 (4H, q, J=7.1 Hz), 2.60 (2H, t, J=7.0 Hz), 2.29 (3H, s), 1.83-1.97 (4H, m), 1.06 (6H, t, J=7.2 Hz)

Mass spectrometric value (ESI-MS) 592, 593, 594 (M−1) 638 (M+2×23)

Compound 1058 3-{[(2-Diethylamino-ethyl)-methyl-amino]-methyl}-N-[4-(4-fluoro-butoxy)-2-(4-methyl-benzylidene-hydrazinocarbonyl)-phenyl]-benzamide

The title compound 1058 was produced in substantially the same manner as in Example S.

¹H-NMR (CD₃OD, 400 MHz): δ 8.42 (1H, d, J=9.0 Hz), 8.32 (1H, s), 7.95 (1H, s), 7.86-7.92 (1H, m), 7.71 (2H, d, J=8.1 Hz), 7.58 (1H, d, J=7.6 Hz), 7.51 (1H, dd, J=7.7 Hz, J=7.7 Hz), 7.41 (1H, d, J=2.7 Hz), 7.25 (2H, d, J=7.8 Hz), 7.19 (1H, dd, J=2.9 Hz, J=9.0 Hz), 4.55-4.60 (1H, m), 4.45 (1H, t, J=5.6 Hz), 4.11 (2H, t, J=5.7 Hz), 3.66 (2H, s), 2.72-2.79 (2H, m), 2.54-2.68 (6H, m), 2.37 (3H, s), 2.28 (3H, s), 1.80-1.95 (4H, m), 1.04 (6H, t, J=7.2 Hz)

Mass spectrometric value (ESI-MS) 588, 589, 590 (M−1) 634, 635 (M+2×23)

Compound 1059 3-{[(2-Diethylamino-ethyl)-methyl-amino]-methyl}-N-[2-(3,4-dimethyl-benzyl idene-hydrazinocarbonyl)-4-(4-fluoro-butoxy)-phenyl]-benzamide

The title compound 1059 was produced in substantially the same manner as in Example S.

¹H-NMR (CD₃OD, 400 MHz): δ 8.43 (1H, d, J=9.0 Hz), 8.28 (1H, s), 7.96 (1H, bs), 7.88-7.92 (1H, m), 7.63 (1H, s), 7.48-7.62 (3H, m), 7.40 (1H, d, J=2.7 Hz), 7.17-7.23 (2H, m), 4.55-4.60 (1H, m), 4.45 (1H, t, J=5.7 Hz), 4.12 (2H, t, J=5.9 Hz), 3.67 (2H, s), 2.72-2.80 (2H, m), 2.55-2.68 (6H, m), 2.30 (3H, s), 2.29 (3H, s), 2.28 (3H, s), 1.80-1.95 (4H, m), 1.03 (6H, t, J=7.2 Hz)

Mass spectrometric value (ESI-MS) 602, 603 (M−1) 642, 648 (M+2×23)

Compound 1060 N-[2-(4-Chloro-3-trifluoromethyl-benzylidene-hydrazinocarbonyl)-4-(4-fluoro-butoxy)-phenyl]-3-{[(2-diethylamino-ethyl)-methyl-amino]-methyl}-benzamide

The title compound 1060 was produced in substantially the same manner as in Example S.

¹H-NMR (CD₃OD, 400 MHz): δ 8.36-8.42 (2H, m), 8.31 (1H, s), 7.98-8.03 (1H, m), 7.95 (1H, s), 7.86-7.91 (1H, m), 7.67 (1H, d, J=8.3 Hz), 7.58 (1H, d, J=7.6 Hz), 7.51 (1H, dd, J=7.6 Hz, J=7.6 Hz), 7.42 (1H, d, J=2.9 Hz), 7.20 (1H, dd, J=2.9 Hz, J=9.0 Hz), 4.55-4.60 (1H, m), 4.45 (1H, t, J=5.7 Hz), 4.12 (2H, t, J=5.9 Hz), 3.66 (2H, s), 2.54-2.78 (8H, m), 2.27 (3H, s), 1.80-1.95 (4H, m), 1.03 (6H, t, J=7.2 Hz)

Mass spectrometric value (ESI-MS) 676, 677, 679 (M−1)

Compound 1061 3-{[(2-Diethylamino-ethyl)-methyl-amino]-methyl}-N-[4-(4-fluoro-butoxy)-2-(4-methoxy-benzylidene-hydrazinocarbonyl)-phenyl]-benzamide

The title compound 1061 was produced in substantially the same manner as in Example S.

¹H-NMR (CD₃OD, 400 MHz): δ 8.43 (1H, d, J=9.3 Hz), 8.29 (1H, s), 7.95 (1H, bs), 7.87-7.92 (1H, m), 7.77 (2H, d, J=8.8 Hz), 7.56-7.61 (1H, m), 7.50 (1H, dd, J=7.6 Hz, J=7.6 Hz), 7.40 (1H, d, J=2.9 Hz), 7.19 (1H, dd, J=2.7 Hz, J=9.0 Hz), 6.97 (2H, d, J=8.8 Hz), 4.55-4.59 (1H, m), 4.45 (1H, t, J=5.7 Hz), 4.11 (2H, t, J=6.0 Hz), 3.83 (3H, s), 3.66 (2H, s), 2.54-2.77 (8H, m), 2.28 (3H, s), 1.80-1.97 (4H, m), 1.03 (6H, t, J=7.2 Hz)

Mass spectrometric value (ESI-MS) 604, 605, 606 (M−1) 606 (M+1) 628, 629 (M+23)

Compound 1062 N-[2-(4-Chloro-3-trifluoromethyl-benzylidene-hydrazinocarbonyl)-4-(4-hydroxy-piperidin-1-yl)-phenyl]-3-(2-hydroxy-ethylsulfanylmethyl)-benzamide

The title compound 1062 was produced in substantially the same manner as in Example F.

¹H-NMR (CD₃OD, 400 MHz): δ 1.67 (2H, m), 2.00 (2H, m), 2.57 (2H, m), 2.99 (2H, m), 3.68 (4H, m), 3.80 (1H, m), 3.86 (2H, s), 7.25 (1H, m), 7.41 (1H, d, J=3.0 Hz), 7.49 (1H, m), 7.59 (1H, m), 7.69 (1H, d, J=8.6 Hz), 7.85 (1H, m), 7.92 (1H, m), 8.05 (1H, m), 8.34 (2H, m), 8.38 (1H, s)

Mass spectrometric value (ESI-MS) 633 (M−1)

Compound 1063 N-[2-(4-Chloro-3-trifluoromethyl-benzylidene-hydrazinocarbonyl)-4-(4-hydroxymethyl-piperidin-1-yl)-phenyl]-3-(2-hydroxy-ethylsulfanylmethyl)-benzamide

The title compound 1063 was produced in substantially the same manner as in Example F.

¹H-NMR (CD₃OD, 400 MHz): δ 1.39 (2H, m), 1.63 (1H, m), 1.88 (2H, m), 2.57 (2H, t, J=6.8 Hz), 2.76 (2H, m), 3.47 (2H, d, J=6.3 Hz), 3.68 (2H, t, J=6.8 Hz), 3.81 (2H, m), 3.86 (2H, s), 7.24 (1H, dd, J=9.2 Hz, J=2.8 Hz), 7.39 (1H, d, J=2.7 Hz), 7.49 (1H, dd, J=7.7 Hz, J=7.7 Hz), 7.58 (1H, d, J=7.6 Hz), 7.67 (1H, d, J=8.3 Hz), 7.84 (1H, d, J=7.6 Hz), 7.91 (1H, s), 8.03 (1H, m), 8.33 (2H, m), 8.37 (1H, s)

Mass spectrometric value (ESI-MS) 647 (M−1)

Compound 1064 N-[2-(3,4-Dimethyl-benzylidene-hydrazinocarbonyl)-4-morpholin-4-yl-phenyl]-3-(2-hydroxy-ethylsulfanylmethyl)-benzamide

The title compound 1064 was produced in substantially the same manner as in Example F.

¹H-NMR (CD₃OD, 400 MHz): δ 2.30 (3H, s), 2.31 (3H, s), 2.57 (2H, m), 3.24 (4H, m), 3.68 (2H, m), 3.87 (6H, m), 7.21 (2H, m), 7.38 (1H, s), 7.45-7.62 (3H, m), 7.66 (1H, m), 7.83-7.96 (2H, m), 8.28 (1H, s), 8.40 (1H, m)

Mass spectrometric value (ESI-MS) 545 (M−1)

Compound 1065 N-[2-(4-Chloro-3-trifluoromethyl-benzylidene-hydrazinocarbonyl)-4-morpholin-4-yl-phenyl]-3-(2-hydroxy-ethylsulfanylmethyl)-benzamide

The title compound 1065 was produced in substantially the same manner as in Example F.

¹H-NMR (DMSO-d₆, 400 MHz): δ 2.50 (2H, m), 3.20 (4H, m), 3.54 (2H, m), 3.78 (4H, m), 3.84 (2H, s), 7.24 (1H, d, J=8.1 Hz), 7.32 (1H, s), 7.53 (2H, m), 7.75-7.84 (2H, m), 7.87 (1H, s), 8.05 (1H, d, J=7.8 Hz), 8.20 (1H, s), 8.25 (1H, d, J=9.0 Hz), 8.48 (1H, s), 11.25 (1H, bs), 12.24 (1H, s)

Mass spectrometric value (ESI-MS) 619 (M−1)

Compound 1066 3-(2-Hydroxy-ethylsulfanylmethyl)-N-[2-(4-methoxy-benzylidene-hydrazinocarbonyl)-4-morpholin-4-yl-phenyl]-benzamide

The title compound 1066 was produced in substantially the same manner as in Example F.

¹H-NMR (CD₃OD, 400 MHz): δ 2.57 (2H, m), 3.30 (4H, m), 3.68 (2H, m), 3.86 (9H, m), 7.00 (2H, m), 7.24 (1H, m), 7.38 (1H, m), 7.49 (1H, m), 7.60 (1H, m), 7.75-7.95 (4H, m), 8.29 (1H, s), 8.42 (1H, m)

Mass spectrometric value (ESI-MS) 547 (M−1)

Compound 1067 N-[4-[1,4′]Bipiperazinyl-1′-yl-2-(4-chloro-3-trifluoromethyl-benzylidene-hydrazinocarbonyl)-phenyl]-3-(2-hydroxy-ethylsulfanylmethyl)-benzamide

The title compound 1067 was produced in substantially the same manner as in Example F.

¹H-NMR (CD₃OD, 400 MHz): δ 1.60 (2H, m), 1.77 (6H, m), 2.11 (2H, m), 2.57 (2H, t, J=6.8 Hz), 2.75-3.02 (7H, m), 3.68 (2H, t, J=6.7 Hz), 3.86 (2H, s), 3.93 (2H, m), 7.26 (1H, m), 7.40 (1H, m), 7.49 (1H, m), 7.59 (1H, m), 7.68 (1H, d, J=8.1 Hz), 7.84 (1H, d, J=8.0 Hz), 7.92 (1H, s), 8.04 (1H, d, J=9.3 Hz), 8.30-8.40 (3H, m),

Mass spectrometric value (ESI-MS) 700 (M−1)

Compound 1068 N-[4-[1,4′]Bipiperazinyl-1′-yl-2-(4-methoxy-benzylidene-hydrazinocarbonyl)-phenyl]-3-(2-hydroxy-ethylsulfanyl-methyl)-benzamide

The title compound 1068 was produced in substantially the same manner as in Example F.

¹H-NMR (DMSO-d₆, 400 MHz): δ 1.39 (2H, m), 1.45-1.65 (6H, m), 1.84 (2H, m), 2.50 (7H, m), 2.70 (2H, m), 3.54 (2H, m), 3.83 (7H, m), 4.78 (1H, t, J=5.6 Hz), 7.02 (2H, d, J=8.8 Hz), 7.19 (1H, m), 7.31 (1H, m), 7.53 (2H, m), 7.70 (2H, d, J=7.8 Hz), 7.76 (1H, d, J=7.3 Hz), 7.86 (1H, s), 8.31 (1H, d, J=9.0 Hz), 8.39 (1H, s), 11.67 (1H, s), 11.88 (1H, s)

Mass spectrometric value (ESI-MS) 628 (M−1)

Compound 1069 N-[2-(3,4-Dimethyl-benzylidene-hydrazinocarbonyl)-4-(4-methyl-piperidin-1-yl)-phenyl]-3-(2-hydroxy-ethylsulfanylmethyl)-benzamide

The title compound 1069 was produced in substantially the same manner as in Example F.

¹H-NMR (DMSO-d₆, 400 MHz): δ 0.97 (3H, d, J=6.6 Hz), 1.27 (2H, m), 1.53 (1H, m), 1.74 (2H, m), 2.27 (3H, s), 2.28 (3H, s), 2.50 (2H, m), 2.70 (2H, m), 3.54 (2H, m), 3.75 (2H, m), 3.85 (2H, s), 4.77 (1H, t, J=5.7 Hz), 7.21 (2H, m), 7.31 (1H, m), 7.45 (1H, d, J=7.6 Hz), 7.52 (3H, m), 7.76 (1H, d, J=7.3 Hz), 7.87 (1H, s), 8.29 (1H, m), 8.37 (1H, s), 11.41 (1H, s), 11.90 (1H, s)

Mass spectrometric value (ESI-MS) 557 (M−1)

Compound 1070 N-[2-(4-Chloro-3-trifluoromethyl-benzylidene-hydrazinocarbonyl)-4-(4-methyl-piperidin-1-yl)-phenyl]-3-(2-hydroxy-ethylsulfanylmethyl)-benzamide

The title compound 1070 was produced in substantially the same manner as in Example F.

¹H-NMR (DMSO-d₆, 400 MHz): δ 0.96 (3H, d, J=6.3 Hz), 1.27 (2H, m), 1.53 (1H, m), 1.74 (2H, m), 2.50 (2H, m), 2.70 (2H, m), 3.54 (2H, m), 3.74 (2H, m), 3.84 (2H, s), 4.83 (1H, m), 7.19 (1H, d, J=8.6 Hz), 7.33 (1H, s), 7.52 (2H, m), 7.79 (2H, m), 7.86 (1H, s), 8.04 (1H, d, J=7.6 Hz), 8.23 (2H, m), 8.49 (1H, s), 12.24 (1H, s)

Mass spectrometric value (ESI-MS) 631 (M−1)

Compound 1071 3-(2-Hydroxy-ethylsulfanylmethyl)-N-[2-(4-methoxy-benzylidene-hydrazinocarbonyl)-4-(4-methyl-piperidin-1-yl)-phenyl]-benzamide

The title compound 1071 was produced in substantially the same manner as in Example F.

¹H-NMR (CD₃OD, 400 MHz): δ 1.01 (3H, d, J=6.1 Hz), 1.37 (2H, m), 1.55 (1H, m), 1.80 (2H, m), 2.57 (2H, t, J=6.7 Hz), 2.76 (2H, m), 3.68 (2H, m), 3.76 (2H, m), 3.84 (3H, s), 3.86 (2H, s), 6.99 (2H, d, J=8.8 Hz), 7.22 (1H, m), 7.38 (1H, m), 7.49 (1H, m), 7.58 (1H, m), 7.79 (2H, d, J=8.5 Hz), 7.85 (1H, d, J=7.6 Hz), 7.92 (1H, s), 8.30 (1H, s), 8.36 (1H, d, J=9.3 Hz)

Mass spectrometric value (ESI-MS) 559 (M−1)

Compound 1072 N-[2-(4-Chloro-3-trifluoromethyl-benzylidene-hydrazinocarbonyl)-4-(4-methyl-piperazin-1-yl)-phenyl]-3-(2-hydroxy-ethylsulfanylmethyl)-benzamide

The title compound 1072 was produced in substantially the same manner as in Example F.

¹H-NMR (CD₃OD, 400 MHz): δ 2.44 (3H, m), 2.56 (2H, m), 2.74 (4H, m), 3.30 (4H, m), 3.66 (2H, m), 3.85 (2H, m), 7.26 (1H, m), 7.40 (1H, s), 7.49 (1H, m), 7.58 (1H, m), 7.68 (1H, m), 7.83 (1H, m), 7.91 (1H, s), 8.02 (1H, m), 8.35 (3H, m)

Mass spectrometric value (ESI-MS) 632 (M−1)

Compound 1073 3-(2-Hydroxy-ethylsulfanylmethyl)-N-[2-(4-methoxy-benzylidene-hydrazinocarbonyl)-4-(4-methyl-piperazin-1-yl)-phenyl]-benzamide

The title compound 1073 was produced in substantially the same manner as in Example F.

¹H-NMR (CD₃OD, 400 MHz): δ 2.34 (3H, s), 2.57 (2H, t, J=6.8 Hz), 2.66 (4H, m), 3.31 (4H, m), 3.68 (2H, t, J=6.8 Hz), 3.84 (3H, s), 3.86 (2H, s), 6.99 (2H, d, J=8.8 Hz), 7.24 (1H, dd, J=9.1 Hz, J=2.7 Hz), 7.38 (1H, d, J=2.9 Hz), 7.49 (1H, d, J=7.7 Hz), 7.59 (1H, d, J=7.6 Hz), 7.79 (2H, d, J=8.8 Hz), 7.85 (1H, d, J=7.8 Hz), 7.92 (1H, s), 8.29 (1H, s), 8.40 (1H, d, J=9.0 Hz)

Mass spectrometric value (ESI-MS) 560 (M−1)

Compound 1074 3-{[(2-Diethylamino-ethyl)-methyl-amino]-methyl}-N-[2-(3,4-dimethyl-benzylidene-hydrazinocarbonyl)-4-morpholin-4-yl-phenyl]-benzamide

The title compound 1074 was produced in substantially the same manner as in Example F.

¹H-NMR (CDCl₃, 400 MHz): δ 1.04 (6H, t, J=7.1 Hz), 2.28 (9H, m), 2.59 (6H, m), 2.68 (2H, m), 2.85 (4H, m), 3.41 (4H, m), 3.64 (2H, s), 6.83 (1H, d, J=9.0 Hz), 6.97 (1H, s), 7.18 (1H, d, J=7.6 Hz), 7.47 (1H, dd, J=7.6 Hz, J=7.6 Hz), 7.56 (2H, m), 7.69 (1H, s), 7.89 (1H, d, J=7.6 Hz), 8.00 (1H, s), 8.09 (1H, d, J=9.0 Hz), 8.55 (1H, s), 11.22 (1H, s)

Mass spectrometric value (ESI-MS) 597 (M−1)

Compound 1075 N-[2-(4-Chloro-3-trifluoromethyl-benzylidene-hydrazinocarbonyl)-4-morpholin-4-yl-phenyl]-3-{[(2-diethylamino-ethyl)-methyl-amino]-methyl}-benzamide

The title compound 1075 was produced in substantially the same manner as in Example F.

¹H-NMR (CDCl₃, 400 MHz): δ 1.03 (6H, t, J=7.1 Hz), 2.28 (3H, s), 2.57 (6H, m), 2.66 (2H, m), 2.80 (4H, m), 3.34 (4H, m), 3.65 (2H, s), 6.80 (1H, d, J=8.6 Hz), 6.89 (1H, s), 7.50 (1H, m), 7.60 (2H, m), 7.89 (1H, d, J=7.6 Hz), 7.97 (1H, m), 8.03 (1H, s), 8.08 (1H, d, J=8.3 Hz), 8.13 (1H, s), 8.66 (1H, s), 11.08 (1H, s)

Mass spectrometric value (ESI-MS) 671 (M−1)

Compound 1076 3-{[(2-Diethylamino-ethyl)-methyl-amino]-methyl}-N42-(4-methoxy-benzylidene-hydrazinocarbonyl)-4-morpholin-4-yl-phenyl)-benzamide

The title compound 1076 was produced in substantially the same manner as in Example F.

¹H-NMR (CDCl₃, 400 MHz): δ 1.06 (6H, t, J=7.1 Hz), 2.25 (3H, s), 2.62 (6H, m), 2.72 (2H, m), 2.91 (4H, m), 3.46 (4H, m), 3.62 (2H, s), 3.82 (3H, s), 6.84-6.92 (3H, m), 7.07 (1H, s), 7.44 (1H, dd, J=7.7 Hz, J=7.7 Hz), 7.53 (1H, m), 7.75 (2H, d, J=8.5 Hz), 7.88 (1H, d, J=7.8 Hz), 7.97 (1H, s), 8.17 (1H, d, J=9.0 Hz), 8.57 (1H, s), 11.34 (1H, s)

Mass spectrometric value (ESI-MS) 599 (M−1)

Example U Compound 1077 N-Benzoyloxy-5-chloro-2-(3-diethylaminomethyl-benzoylamino)-benzamide

2-Amino-5-chloro-benzoic acid methyl ester (1.5 g) was dissolved in anhydrous methylene chloride (25 ml). Pyridine (1.4 ml) and 3-(chloromethyl)benzoyl chloride (1.4 ml) were added dropwise to the solution at 0° C., and the mixture was then stirred at room temperature for 30 min. After the completion of the reaction, distilled water was added thereto at room temperature, and the mixture was subjected to separatory extraction with chloroform. The organic layer was then washed with saturated brine, was dried over sodium sulfate, and was then concentrated under the reduced pressure to precipitate crystals. The precipitated crystals were collected by filtration through Kiriyama Rohto and were washed with ether to give 5-chloro-2-(3-chloromethyl-benzoylamino)-benzoic acid methyl ester as a useful intermediate (2.4 g, yield 90%).

5-Chloro-2-(3-chloromethyl-benzoylamino)-benzoic acid methyl ester (2.4 g) produced by the above process was dissolved in anhydrous methylene chloride (30 ml). Triethylamine (1.5 ml) and diethylamine (2.0 ml) were added dropwise to the solution at room temperature, and the mixture was then stirred at that temperature for 48 hr. After the completion of the reaction, the reaction system was concentrated under the reduced pressure, and the residue was purified by column chromatography eluted with a chloroform-methanol system to give 5-chloro-2-(3-diethylaminomethyl-benzoylamino)-benzoic acid methyl ester as a useful intermediate (1.9 g, yield 71%).

Subsequently, 5-chloro-2-(3-diethylaminomethyl-benzoylamino)-benzoic acid methyl ester (1.9 g) produced by the above process was dissolved in tetrahydrofuran/distilled water=4/1 (20 ml). Lithium hydroxide monohydrate (420 mg) was added to the solution at room temperature, and the mixture was then stirred at that temperature for 2.5 hr. After the completion of the reaction, the reaction system was concentrated under the reduced pressure, and the residue was purified by column chromatography eluted with a chloroform-methanol system to give 5-chloro-2-(3-diethylaminomethyl-benzoylamino)-benzoic acid (1.0 g, yield 56%).

5-Chloro-2-(3-diethylaminomethyl-benzoylamino)-benzoic acid (50 mg) produced by the above process was dissolved in N,N-dimethylformamide (1.0 ml). 1-(3-Dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (38 mg), 1-hydroxy-benzotriazole monohydrate (28 mg), triethylamine (50 μl) and o-benzyl-hydroxylamine hydrochloride (40 mg) were added to the solution at room temperature, and the mixture was then stirred at that temperature for 24 hr. After the completion of the reaction, distilled water was added thereto at room temperature, and the mixture was subjected to separatory extraction with ethyl acetate. The organic layer was washed with saturated brine, was dried over sodium sulfate, and was then concentrated under the reduced pressure. The residue was purified by column chromatography eluted with a chloroform-methanol system to give the title compound 1077 (29 mg, yield 45%).

¹H-NMR (CD₃OD, 400 MHz): δ 8.55 (1H, d, J=9.0 Hz), 7.98 (1H, s), 7.87-7.91 (1H, m), 7.61-7.65 (2H, m), 7.40-7.56 (4H, m), 7.23-7.38 (3H, m), 4.99 (2H, s), 3.89 (2H, s), 2.73 (4H, q, J=7.2 Hz), 1.15 (6H, t, J=7.2 Hz)

Mass spectrometric value (ESI-MS) 463, 465, 466 (M−1) 465, 467 (M+1) 489 (M+23)

Starting compounds for compounds 1 to 1076 are shown in Table 1. In the table, compounds A, B, C, and B′ correspond to compounds described in Examples 1 to 11 and Examples A to T and schemes 1 and 2.

TABLE 1 A B C B′ Compound 1 Methyl 2-amino- 3,4-Dimethoxy- Trans- benzoate benzoyl chloride cinnamaldehyde Compound 2 Methyl 2-amino- 3,4-Dimethoxy- 2-Fluoro- benzoate benzoyl chloride benzaldehyde Compound 3 Methyl 2-amino- 3,4-Dimethoxy- o-Tolualdehyde benzoate benzoyl chloride Compound 4 Methyl 2-amino- 3,4-Dimethoxy- o-Methoxybenzaldehyde benzoate benzoyl chloride Compound 5 Methyl 2-amino- 3,4-Dimethoxy- m-Methoxy- benzoate benzoyl chloride benzaldehyde Compound 6 Methyl 2-amino- 3,4-Dimethoxy- 3,5-Ditert-butyl- benzoate benzoyl chloride 4-hydroxybenzaldehyde Compound 7 Methyl 2-amino- 3,4-Dimethoxy- α-Methyl- benzoate benzoyl chloride cinnamaldehyde Compound 8 Methyl 2-amino- 3,4-Dimethoxy- 3,5-Ditrifluoro benzoate benzoyl chloride methylbenzaldehyde Compound 9 Methyl 2-amino- 3,4-Dimethoxy- 3-Cyano- benzoate benzoyl chloride benzaldehyde Compound 10 Methyl 2-amino- 3,4-Dimethoxy- 2-Bromo- benzoate benzoyl chloride benzaldehyde Compound 11 Methyl 2-amino- 3,4-Dimethoxy- Vanillin benzoate benzoyl chloride Compound 12 Methyl 2- 3,4-Dimethoxy- 3,4,5- aminobenzoate benzoyl chloride Trimethoxy- benzaldehyde Compound 13 Methyl 2-amino-5- 3,4-Dimethoxy- Trans- bromobenzoate benzoyl chloride cinnamaldehyde Compound 14 Methyl 2-amino-5- 3,4-Dimethoxy- 2-Bromo- bromobenzoate benzoyl chloride benzaldehyde Compound 15 Methyl 2-amino- 3,4-Dimethoxy- 3-Fluoro- benzoate benzoyl chloride benzaldehyde Compound 16 Methyl 2-amino- 3,4-Dimethoxy- 4-Fluoro- benzoate benzoyl chloride benzaldehyde Compound 17 Methyl 2-amino- 3,4-Dimethoxy- Benzaldehyde benzoate benzoyl chloride Compound 18 Methyl 2-amino- 3,4-Dimethoxy- 3-Hydroxy- benzoate benzoyl chloride benzaldehyde Compound 19 Methyl 2-amino- 3,4-Dimethoxy- 4-Hydroxy- benzoate benzoyl chloride benzaldehyde Compound 20 Methyl 2-amino- 3,4-Dimethoxy- m-Tolualdehyde benzoate benzoyl chloride Compound 21 Methyl 2-amino- 3,4-Dimethoxy- Furfural benzoate benzoyl chloride Compound 22 Methyl 2-amino- 3,4-Dimethoxy- 5-Methylfurfural benzoate benzoyl chloride Compound 23 Methyl 2-amino- 3,4-Dimethoxy- 2-Thiophene- benzoate benzoyl chloride carboxyaldehyde Compound 24 Methyl 2-amino- 3,4-Dimethoxy- 3-Thiophene- benzoate benzoyl chloride carboxyaldehyde Compound 25 Methyl 2-amino- 3,4-Dimethoxy- 2,4-Dihydroxy- benzoate benzoyl chloride benzaldehyde Compound 26 Methyl 2-amino- 3,4-Dimethoxy- 3,4-Dihydroxy- benzoate benzoyl chloride benzaldehyde Compound 27 Methyl 2-amino- 2-Fluorobenzoyl Benzaldehyde benzoate chloride Compound 28 Methyl 2-amino-5- 3,4-Dimethoxy- 2-Fluoro- bromobenzoate benzoyl chloride benzaldehyde Compound 29 Methyl 2-amino-5- 3,4-Dimethoxy- 3-Fluoro- bromobenzoate benzoyl chloride benzaldehyde Compound 30 Methyl 2-amino-5- 3,4-Dimethoxy- o-Tolualdehyde bromobenzoate benzoyl chloride Compound 31 Methyl 2-amino-5- 3,4-Dimethoxy- m-Tolualdehyde bromobenzoate benzoyl chloride Compound 32 Methyl 2-amino- 3,4-Dimethoxy- 3-Chloro-4- benzoate benzoyl chloride fluoro- benzaldehyde Compound 33 Methyl 2-amino- 3,4-Dimethoxy- 4-Trifluoro- benzoate benzoyl chloride methoxybenzaldehyde Compound 34 Methyl 2-amino- 3,4-Dimethoxy- 3-Bromo-4- benzoate benzoyl chloride methoxybenzaldehyde Compound 35 Methyl 2-amino- 3,4-Dimethoxy- 3-Chlorobenzaldehyde benzoate benzoyl chloride Compound 36 Methyl 2-amino- 3,4-Dimethoxy- 3,5-Dimethyl-4- benzoate benzoyl chloride hydroxybenzaldehyde Compound 37 Methyl 2-amino- 3,4-Dimethoxy- 3-Ethoxy-4- benzoate benzoyl chloride hydroxybenzaldehyde Compound 38 Methyl 2-amino- 2-Fluorobenzoyl 4-Fluorobenzaldehyde benzoate chloride Compound 39 Methyl 2-amino- 2-Fluorobenzoyl 3-Hydroxy- benzoate chloride benzaldehyde Compound 40 Methyl 2-amino- 2-Fluorobenzoyl p-Tolualdehyde benzoate chloride Compound 41 Methyl 2-amino- 3,4-Dimethoxy- 4-Chloro-3-tri- benzoate benzoyl chloride fluoromethyl- benzaldehyde Compound 42 Methyl 2-amino- 3,4-Dimethoxy- 4-Hydroxy-3- benzoate benzoyl chloride methylbenzaldehyde Compound 43 Methyl 2-amino- 3,4-Dimethoxy- 2,5-Dimethyl- benzoate benzoyl chloride benzaldehyde Compound 44 Methyl 2-amino- 3,4-Dimethoxy- 2-Fluoro-5-tri- benzoate benzoyl chloride fluoromethyl- benzaldehyde Compound 45 Methyl 2-amino- 2-Fluorobenzoyl 4-Hydroxy-3- benzoate chloride methylbenzaldehyde Compound 46 Methyl 2-amino- 2-Fluorobenzoyl 2,5-Dimethyl- benzoate chloride benzaldehyde Compound 47 Methyl 2-amino- 4-Methoxybenzoyl 3-Fluorobenzaldehyde benzoate chloride Compound 48 Methyl 2-amino- 4-Methoxybenzoyl 4-Fluorobenzaldehyde benzoate chloride Compound 49 Methyl 2-amino- 4-Methoxybenzoyl m-Tolualdehyde benzoate chloride Compound 50 Methyl 2-amino- 4-Methoxybenzoyl 3-Hydroxybenzaldehyde benzoate chloride Compound 51 Methyl 2-amino- 4-Methoxybenzoyl p-Tolualdehyde benzoate chloride Compound 52 Methyl 2-amino- 3,4-Dimethoxy- 4-Allyloxybenzaldehyde benzoate benzoyl chloride Compound 53 Methyl 2-amino- 3,4-Dimethoxy- 3,5-Dimethoxy- benzoate benzoyl chloride benzaldehyde Compound 54 Methyl 2-amino- 3,4-Dimethoxy- 3-[3-(Trifluoro- benzoate benzoyl chloride methyl)phenoxy]- benzaldehyde Compound 55 Methyl 2-amino- 3,5-Dimethoxy- 3-Fluorobenzaldehyde benzoate benzoyl chloride Compound 56 Methyl 2-amino- 3,5-Dimethoxy- 4-Fluorobenzaldehyde benzoate benzoyl chloride Compound 57 Methyl 2-amino- 3,5-Dimethoxy- p-Tolualdehyde benzoate benzoyl chloride Compound 58 Methyl 2-amino- 3,5-Dimethoxy- 3-Hydroxybenzaldehyde benzoate benzoyl chloride Compound 59 Methyl 2-amino-5- 3,4-Dimethoxy- 3-Chlorobenzaldehyde bromobenzoate benzoyl chloride Compound 60 Methyl 2-amino-5- 3,4-Dimethoxy- 4-Chlorobenzaldehyde bromobenzoate benzoyl chloride Compound 61 Methyl 2-amino-5- 3,4-Dimethoxy- 4-Fluorobenzaldehyde bromobenzoate benzoyl chloride Compound 62 Methyl 2-amino-5- 3,4-Dimethoxy- p-Tolualdehyde bromobenzoate benzoyl chloride Compound 63 Methyl 2-amino-5- 3,4-Dimethoxy- 3-Hydroxybenzaldehyde bromobenzoate benzoyl chloride Compound 64 Methyl 2-amino-5- 3,4-Dimethoxy- 4-Hydroxy- bromobenzoate benzoyl chloride benzaldehyde Compound 65 Methyl 2-amino-5- 3,4-Dimethoxy- 3-Fluorobenzaldehyde chlorobenzoate benzoyl chloride Compound 66 Methyl 2-amino-5- 3,4-Dimethoxy- 4-Fluorobenzaldehyde chlorobenzoate benzoyl chloride Compound 67 Methyl 2-amino-5- 3,4-Dimethoxy- m-Tolualdehyde chlorobenzoate benzoyl chloride Compound 68 Methyl 2-amino-5- 3,4-Dimethoxy- p-Tolualdehyde chlorobenzoate benzoyl chloride Compound 69 Methyl 2-amino-5- 3,4-Dimethoxy- 3-Hydroxybenzaldehyde chlorobenzoate benzoyl chloride Compound 70 Methyl 2-amino-5- 3,4-Dimethoxy- 4-Hydroxybenzaldehyde chlorobenzoate benzoyl chloride Compound 71 Methyl 2-amino-4- 3,4-Dimethoxy- 3-Fluorobenzaldehyde chlorobenzoate benzoyl chloride Compound 72 Methyl 2-amino-4- 3,4-Dimethoxy- 4-Fluorobenzaldehyde chlorobenzoate benzoyl chloride Compound 73 Methyl 2-amino-4- 3,4-Dimethoxy- m-Tolualdehyde chlorobenzoate benzoyl chloride Compound 74 Methyl 2-amino-4- 3,4-Dimethoxy- p-Tolualdehyde chlorobenzoate benzoyl chloride Compound 75 Methyl 2-amino-4- 3,4-Dimethoxy- 3-Hydroxybenzaldehyde chlorobenzoate benzoyl chloride Compound 76 Methyl 2-amino- 4-Fluorobenzoyl 3-Fluorobenzaldehyde benzoate chloride Compound 77 Methyl 2-amino- 4-Fluorobenzoyl 4-Fluorobenzaldehyde benzoate chloride Compound 78 Methyl 2-amino- 4-Fluorobenzoyl m-Tolualdehyde benzoate chloride Compound 79 Methyl 2- 4-Fluorobenzoyl p-Tolualdehyde aminobenzoate chloride Compound 80 Methyl 2-amino- 4-Fluorobenzoyl 3-Hydroxybenzaldehyde benzoate chloride Compound 81 Methyl 2-amino- 3-Fluorobenzoyl 3-Fluorobenzaldehyde benzoate chloride Compound 82 Methyl 2-amino- 3-Fluorobenzoyl 4-Fluorobenzaldehyde benzoate chloride Compound 83 Methyl 2-amino- 3-Fluorobenzoyl m-Tolualdehyde benzoate chloride Compound 84 Methyl 2-amino- 3-Fluorobenzoyl p-Tolualdehyde benzoate chloride Compound 85 Methyl 2-amino- 3-Fluorobenzoyl 3-Hydroxy- benzoate chloride benzaldehyde Compound 86 Methyl 2-amino- 3-Fluorobenzoyl 4-Hydroxy- benzoate chloride benzaldehyde Compound 87 Methyl 2-amino-5- 3,4-Dimethoxy- 4-Chloro-3-tri- bromobenzoate benzoyl chloride fluoromethylbenzaldehyde Compound 88 Methyl 2-amino-5- 3,4-Dimethoxy- 4-Chloro-3-tri- chlorobenzoate benzoyl chloride fluoromethyl- benzaldehyde Compound 89 Methyl 2-amino- 3,5-Dimethoxy- 4-Chloro-3-tri- benzoate benzoyl chloride fluoromethyl- benzaldehyde Compound 90 Methyl 2-amino- 4-Methoxybenzoyl 4-Chloro-3-tri- benzoate chloride fluoromethyl- benzaldehyde Compound 91 Methyl 2-amino-5- 3,4-Dimethoxy- 3,4-Dimethyl- bromobenzoate benzoyl chloride benzaldehyde Compound 92 Methyl 2-amino-5- 3,4-Dimethoxy- 3,4-Dimethyl- chlorobenzoate benzoyl chloride benzaldehyde Compound 93 Methyl 2- 3,5-Dimethoxy- 3,4-Dimethyl- aminobenzoate benzoyl chloride benzaldehyde Compound 94 Methyl 2- 4-Methoxy- 3,4-Dimethyl- aminobenzoate benzoyl chloride benzaldehyde Compound 95 Methyl 2- 3-Fluorobenzoyl 3,4-Dimethyl- aminobenzoate chloride benzaldehyde Compound 96 Methyl 2- 4-Fluorobenzoyl 3,4-Dimethyl- aminobenzoate chloride benzaldehyde Compound 97 Methyl 2-amino-5- 3,4-Dimethoxy- 3-Bromo-4- bromobenzoate benzoyl chloride methoxy- benzaldehyde Compound 98 Methyl 2-amino-5- 3,4-Dimethoxy- 3-Bromo-4- chlorobenzoate benzoyl chloride methoxy- benzaldehyde Compound 99 Methyl 2-amino- 3,5-Dimethoxy- 3-Bromo-4- benzoate benzoyl chloride methoxy- benzaldehyde Compound 100 Methyl 2-amino- 4-Methoxybenzoyl 3-Bromo-4- benzoate chloride methoxybenzaldehyde Compound 101 Methyl 2-amino- 3-Fluorobenzoyl 3-Bromo-4- benzoate chloride methoxy- benzaldehyde Compound 102 Methyl 2-amino- 4-Fluorobenzoyl 3-Bromo-4- benzoate chloride methoxy- benzaldehyde Compound 103 Methyl 2-amino- 3,4-Dimethoxy- 3-Nitro- benzoate benzoyl chloride benzaldehyde Compound 104 Methyl 2-amino- 3,4-Dimethoxy- 4-Dimethyl- benzoate benzoyl chloride aminobenzaldehyde Compound 105 Methyl 2-amino-5- 4-Fluorobenzoyl 3-Fluorobenzaldehyde bromobenzoate chloride Compound 106 Methyl 2-amino-5- 4-Fluorobenzoyl 4-Fluorobenzaldehyde bromobenzoate chloride Compound 107 Methyl 2-amino-5- 4-Fluorobenzoyl 3-Chlorobenzaldehyde bromobenzoate chloride Compound 108 Methyl 2-amino-5- 4-Fluorobenzoyl 4-Chlorobenzaldehyde bromobenzoate chloride Compound 109 Methyl 2-amino-5- 4-Fluorobenzoyl 3-Hydroxy- bromobenzoate chloride benzaldehyde Compound 110 Methyl 2-amino-5- 3,4-Dimethoxy- 3-Pyridine- bromobenzoate benzoyl chloride carboxyaldehyde Compound 111 Methyl 2-amino-5- 3,4-Dimethoxy- 3-Pyridine- chlorobenzoate benzoyl chloride carboxyaldehyde Compound 112 Methyl 2-amino- 4-Methoxybenzoyl 3-Pyridine- benzoate chloride carboxyaldehyde Compound 113 Methyl 2-amino- 4-Fluorobenzoyl 3-Pyridine- benzoate chloride carboxyaldehyde Compound 114 Methyl 2-amino-5- 3,5-Dimethoxy- 3-Fluorobenzaldehyde bromobenzoate benzoyl chloride Compound 115 Methyl 2-amino-5- 3,5-Dimethoxy- 4-Fluorobenzaldehyde bromobenzoate benzoyl chloride Compound 116 Methyl 2-amino-5- 3,5-Dimethoxy- 3-Chlorobenzaldehyde bromobenzoate benzoyl chloride Compound 117 Methyl 2-amino-5- 3,5-Dimethoxy- 4-Chlorobenzaldehyde bromobenzoate benzoyl chloride Compound 118 Methyl 2-amino-5- 3,5-Dimethoxy- m-Tolualdehyde bromobenzoate benzoyl chloride Compound 119 Methyl 2-amino-5- 3,5-Dimethoxy- p-Tolualdehyde bromobenzoate benzoyl chloride Compound 120 Methyl 2-amino- 3-Trifluoro- 3-Fluorobenzaldehyde benzoate methoxybenzoyl chloride Compound 121 Methyl 2-amino- 3-Trifluoro- 4-Fluorobenzaldehyde benzoate methoxybenzoyl chloride Compound 122 Methyl 2-amino- 3-Trifluoro- 3-Chlorobenzaldehyde benzoate methoxybenzoyl chloride Compound 123 Methyl 2-amino- 3-Trifluoro- 4-Chloro- benzoate methoxybenzoyl benzaldehyde chloride Compound 124 Methyl 2-amino- 3-Trifluoro- p-Tolualdehyde benzoate methoxybenzoyl chloride Compound 125 Methyl 2-amino-5- 3,4-Dimethoxy- 4-Fluoro- hydroxy-benzoate benzoyl chloride benzaldehyde Compound 126 Methyl 2-amino-5- 3,4-Dimethoxy- 3,4-Dimethoxy- chlorobenzoate benzoyl chloride benzaldehyde Compound 127 Methyl 2-amino-5- 3,4-Dimethoxy- 3,4-Dimethoxy- bromobenzoate benzoyl chloride benzaldehyde Compound 128 Methyl 2-amino-5- 3,5-Dimethoxy- 3,4-Dimethoxy- bromobenzoate benzoyl chloride benzaldehyde Compound 129 Methyl 2-amino- Nicotinoyl chloride 3-Fluoro- benzoate hydrochloride benzaldehyde Compound 130 Methyl 2-amino- Nicotinoyl chloride 4-Fluoro- benzoate hydrochloride benzaldehyde Compound 131 Methyl 2-amino- Nicotinoyl chloride m-Tolualdehyde benzoate hydrochloride Compound 132 Methyl 2-amino- Nicotinoyl chloride p-Tolualdehyde benzoate hydrochloride Compound 133 Methyl 2-amino- Nicotinoyl chloride 3,4-Dimethyl- benzoate hydrochloride benzaldehyde Compound 134 Methyl 2-amino- Isonicotinoyl 3-Fluoro- benzoate chloride benzaldehyde hydrochloride Compound 135 Methyl 2-amino- Isonicotinoyl 4-Fluoro- benzoate chloride benzaldehyde hydrochloride Compound 136 Methyl 2-amino- Isonicotinoyl m-Tolualdehyde benzoate chloride hydrochloride Compound 137 Methyl 2-amino- Isonicotinoyl p-Tolualdehyde benzoate chloride hydrochloride Compound 138 Methyl 2-amino- Isonicotinoyl 3,4-Dimethyl- benzoate chloride benzaldehyde hydrochloride Compound 139 Methyl 2-amino-5- 3,4-Dimethoxy- 4-Fluoro- hydroxybenzoate benzoyl chloride benzaldehyde Compound 140 Methyl 2-amino-5- 3,4-Dimethoxy- 4-Fluoro- hydroxybenzoate benzoyl chloride benzaldehyde Compound 141 Methyl 2-amino-5- 3,4-Dimethoxy- 3-Fluoro- methoxybenzoate benzoyl chloride benzaldehyde Compound 142 Methyl 2-amino-5- 3,4-Dimethoxy- 4-Fluoro- methoxybenzoate benzoyl chloride benzaldehyde Compound 143 Methyl 2-amino-5- 3,4-Dimethoxy- m-Tolualdehyde methoxybenzoate benzoyl chloride Compound 144 Methyl 2-amino-5- 3,4-Dimethoxy- p-Tolualdehyde methoxybenzoate benzoyl chloride Compound 145 Methyl 2-amino-5- 3,4-Dimethoxy- 3,4-Dimethyl- methoxybenzoate benzoyl chloride benzaldehyde Compound 146 Methyl 2-amino-5- 3,4-Dimethoxy- 3-Fluoro- methylbenzoate benzoyl chloride benzaldehyde Compound 147 Methyl 2-amino-5- 3,4-Dimethoxy- 4-Fluoro- methylbenzoate benzoyl chloride benzaldehyde Compound 148 Methyl 2-amino-5- 3,4-Dimethoxy- m-Tolualdehyde methylbenzoate benzoyl chloride Compound 149 Methyl 2-amino-5- 3,4-Dimethoxy- p-Tolualdehyde methylbenzoate benzoyl chloride Compound 150 Methyl 2-amino-5- 3,4-Dimethoxy- 3,4-Dimethyl- methylbenzoate benzoyl chloride benzaldehyde Compound 151 Methyl 2-amino-5- 2-Furoyl chloride 3-Fluoro- bromobenzoate benzaldehyde Compound 152 Methyl 2-amino-5- 2-Furoyl chloride 4-Fluoro- bromobenzoate benzaldehyde Compound 153 Methyl 2-amino-5- 2-Furoyl chloride m-Tolualdehyde bromobenzoate Compound 154 Methyl 2-amino-5- 2-Furoyl chloride p-Tolualdehyde bromobenzoate Compound 155 Methyl 2-amino-5- 2-Furoyl chloride 3,4-Dimethyl- bromobenzoate benzaldehyde Compound 156 Methyl 2-amino-5- 2-Furoyl chloride 4-Chloro-3-tri- bromobenzoate fluoromethyl- benzaldehyde Compound 157 Methyl 2-amino-5- Thiophene-2- 3-Fluorobenzaldehyde bromobenzoate carbonyl chloride Compound 158 Methyl 2-amino-5- Thiophene-2- 4-Fluorobenzaldehyde bromobenzoate carbonyl chloride Compound 159 Methyl 2-amino-5- Thiophene-2- m-Tolualdehyde bromobenzoate carbonyl chloride Compound 160 Methyl 2-amino-5- Thiophene-2- p-Tolualdehyde bromobenzoate carbonyl chloride Compound 161 Methyl 2-amino-5- Thiophene-2- 3,4-Dimethyl- bromobenzoate carbonyl chloride benzaldehyde Compound 162 Methyl 2-amino-5- Thiophene-2- 4-Chloro-3-tri- bromobenzoate carbonyl chloride fluoromethylbenzaldehyde Compound 163 Methyl 2-amino- Isonicotinoyl 3,4-Dimethyl- benzoate chloride benzaldehyde hydrochloride Compound 164 Methyl 2- Nicotinoyl chloride p-Tolualdehyde aminobenzoate hydrochloride Compound 165 Methyl 2- Nicotinoyl chloride 3,4-Dimethyl- aminobenzoate hydrochloride benzaldehyde Compound 166 Methyl 2-amino-5- Isonicotinoyl 3-Fluorobenzaldehyde bromobenzoate chloride hydrochloride Compound 167 Methyl 2-amino-5- Isonicotinoyl 4-Fluorobenzaldehyde bromobenzoate chloride hydrochloride Compound 168 Methyl 2-amino-5- Isonicotinoyl m-Tolualdehyde bromobenzoate chloride hydrochloride Compound 169 Methyl 2-amino-5- Isonicotinoyl p-Tolualdehyde bromobenzoate chloride hydrochloride Compound 170 Methyl 2-amino-5- Isonicotinoyl 3,4-Dimethyl- bromobenzoate chloride benzaldehyde hydrochloride Compound 171 Methyl 2-amino-5- Isonicotinoyl 4-Chloro-3-tri- bromobenzoate chloride fluoromethylbenzaldehyde hydrochloride Compound 172 Methyl 2-amino-5- Nicotinoyl chloride 3-Fluorobenzaldehyde bromobenzoate hydrochloride Compound 173 Methyl 2-amino-5- Nicotinoyl chloride 4-Fluorobenzaldehyde bromobenzoate hydrochloride Compound 174 Methyl 2-amino-5- Nicotinoyl chloride m-Tolualdehyde bromobenzoate hydrochloride Compound 175 Methyl 2-amino-5- Nicotinoyl chloride p-Tolualdehyde bromobenzoate hydrochloride Compound 176 Methyl 2-amino-5- Nicotinoyl chloride 3,4-Dimethyl- bromobenzoate hydrochloride benzaldehyde Compound 177 Methyl 2-amino-5- Nicotinoyl chloride 4-Chloro-3-tri- bromobenzoate hydrochloride fluoromethylbenzaldehyde Compound 178 Methyl 2-amino-5- 4-Ethyl benzoyl 3-Fluorobenzaldehyde bromobenzoate chloride Compound 179 Methyl 2-amino-5- 4-Ethyl benzoyl 4-Fluorobenzaldehyde bromobenzoate chloride Compound 180 Methyl 2-amino-5- 4-Ethyl benzoyl m-Tolualdehyde bromobenzoate chloride Compound 181 Methyl 2-amino-5- 4-Ethyl benzoyl p-Tolualdehyde bromobenzoate chloride Compound 182 Methyl 2-amino-5- 4-Ethyl benzoyl 3,4-Dimethyl- bromobenzoate chloride benzaldehyde Compound 183 Methyl 2-amino-5- 4-Ethyl benzoyl 4-Chloro-3-tri- bromobenzoate chloride fluoromethylbenzaldehyde Compound 184 Methyl 2-amino-5- Nicotinoyl chloride 3-Fluorobenzaldehyde chlorobenzoate hydrochloride Compound 185 Methyl 2-amino-5- Nicotinoyl chloride 4-Fluorobenzaldehyde chlorobenzoate hydrochloride Compound 186 Methyl 2-amino-5- Nicotinoyl chloride m-Tolualdehyde chlorobenzoate hydrochloride Compound 187 Methyl 2-amino-5- Nicotinoyl chloride p-Tolualdehyde chlorobenzoate hydrochloride Compound 188 Methyl 2-amino-5- Nicotinoyl chloride 3,4-Dimethyl- chlorobenzoate hydrochloride benzaldehyde Compound 189 Methyl 2-amino-5- Nicotinoyl chloride 4-Chloro-3-tri- chlorobenzoate hydrochloride fluoromethylbenzaldehyde Compound 190 Methyl 2-amino-5- Isonicotinoyl 4-Fluorobenzaldehyde chlorobenzoate chloride hydrochloride Compound 191 Methyl 2-amino-5- Isonicotinoyl m-Tolualdehyde chlorobenzoate chloride hydrochloride Compound 192 Methyl 2-amino-5- Isonicotinoyl p-Tolualdehyde chlorobenzoate chloride hydrochloride Compound 193 Methyl 2-amino-5- Isonicotinoyl 3,4-Dimethyl- chlorobenzoate chloride benzaldehyde hydrochloride Compound 194 Methyl 2-amino-5- Isonicotinoyl 4-Chloro-3-tri- chlorobenzoate chloride fluoromethylbenzaldehyde hydrochloride Compound 195 Methyl 2-amino-5- 3-(Chloromethyl)- 3-Fluorobenzaldehyde 4-Mercapto- bromobenzoate benzoyl chloride pyridine Compound 196 Methyl 2-amino-5- 3-(Chloromethyl)- 4-Fluorobenzaldehyde 4-Mercapto- bromobenzoate benzoyl chloride pyridine Compound 197 Methyl 2-amino-5- 3-(Chloromethyl)- m-Tolualdehyde 4-Mercapto- bromobenzoate benzoyl chloride pyridine Compound 198 Methyl 2-amino-5- 3-(Chloromethyl)- p-Tolualdehyde 4-Mercapto- bromobenzoate benzoyl chloride pyridine Compound 199 Methyl 2-amino-5- 3-(Chloromethyl)- 3,4-Dimethyl- 4-Mercapto- bromobenzoate benzoyl chloride benzaldehyde pyridine Compound 200 Methyl 2-amino-5- 3-(Chloromethyl)- 4-Chloro-3- 4-Mercapto- bromobenzoate benzoyl chloride trifluoromethyl- pyridine benzaldehyde Compound 201 Methyl 2-amino-5- 3,4-Dimethoxy- 1-Methylpyrrole- bromobenzoate benzoyl chloride 2-carboxaldehyde Compound 202 Methyl 2-amino-5- 3,4-Dimethoxy- 4,5-Dimethyl-2- bromobenzoate benzoyl chloride furancarboxaldehyde Compound 203 Methyl 2-amino- Isonicotinoyl p-Tolualdehyde benzoate chloride hydrochloride Compound 204 Methyl 2-amino-5- 3,4-Dimethoxy- 3-Fluoro- iodobenzoate benzoyl chloride benzaldehyde Compound 205 Methyl 2-amino-5- 3,4-Dimethoxy- 4-Fluoro- iodobenzoate benzoyl chloride benzaldehyde Compound 206 Methyl 2-amino-5- 3,4-Dimethoxy- m-Tolualdehyde iodobenzoate benzoyl chloride Compound 207 Methyl 2-amino-5- 3,4-Dimethoxy- p-Tolualdehyde iodobenzoate benzoyl chloride Compound 208 Methyl 2-amino-5- 3,4-Dimethoxy- 3,4-Dimethyl- iodobenzoate benzoyl chloride benzaldehyde Compound 209 Methyl 2-amino-5- 3,4-Dimethoxy- 4-Chloro-3- iodobenzoate benzoyl chloride trifluoromethyl- benzaldehyde Compound 210 Methyl 2-amino- Isonicotinoyl 1-Methylpyrrole- benzoate chloride 2-carboxaldehyde hydrochloride Compound 211 Methyl 2-amino-5- Nicotinoyl chloride 1-Methylpyrrole- bromobenzoate hydrochloride 2-carboxaldehyde Compound 212 Methyl 2-amino-5- Nicotinoyl chloride 1-Methylpyrrole- chlorobenzoate hydrochloride 2-carboxaldehyde Compound 213 Methyl 2- 3,4-Dimethoxy- 3-Fluoro- aminobenzoate benzoyl chloride acetophenone Compound 214 Methyl 2-amino-5- 3,4-Dimethoxy- 3-Fluoro- bromobenzoate benzoyl chloride acetophenone Compound 215 Methyl 2-amino-5- Nicotinoyl chloride 3-Methyl- bromobenzoate hydrochloride acetophenone Compound 216 Methyl 2-amino-5- Nicotinoyl chloride 4-Methyl- bromobenzoate hydrochloride acetophenone Compound 217 Methyl 2-amino-5- Nicotinoyl chloride 4-Methyl- chlorobenzoate hydrochloride acetophenone Compound 218 Methyl 2- Nicotinoyl chloride 4,5-Dimethyl-2- aminobenzoate hydrochloride furancarboxaldehyde Compound 219 Methyl 2- Isonicotinoyl 4,5-Dimethyl-2- aminobenzoate chloride furancarboxaldehyde hydrochloride Compound 220 Methyl 2-amino-5- Nicotinoyl chloride 4,5-Dimethyl-2- bromobenzoate hydrochloride furancarboxaldehyde Compound 221 Methyl 2-amino-5- Isonicotinoyl 4,5-Dimethyl-2- bromobenzoate chloride furancarboxaldehyde hydrochloride Compound 222 Methyl 2-amino-5- Nicotinoyl chloride 4,5-Dimethyl-2- chlorobenzoate hydrochloride furancarboxaldehyde Compound 223 Methyl 2-amino-5- Isonicotinoyl 4,5-Dimethyl-2- chlorobenzoate chloride furancarboxaldehyde hydrochloride Compound 224 Methyl 2- Benzoyl chloride Benzaldehyde aminobenzoate Compound 225 Methyl 2-amino- Benzoyl chloride 2-Fluoro- benzoate benzaldehyde Compound 226 Methyl 2-amino- Benzoyl chloride 3-Fluoro- benzoate benzaldehyde Compound 227 Methyl 2-amino-3,4- 3,4-Dimethoxy- Benzaldehyde dimethoxy- benzoyl chloride benzoate Compound 228 Methyl 2- Benzoyl chloride 2-Bromo- aminobenzoate benzaldehyde Compound 229 Methyl 2- Benzoyl chloride o-Tolualdehyde aminobenzoate Compound 230 Methyl 2-amino-3,4- 3,4-Dimethoxy- o-Tolualdehyde dimethoxy- benzoyl chloride benzoate Compound 231 Methyl 2-amino- 3,4-Dimethoxy- 2-Chloro- benzoate benzoyl chloride benzaldehyde Compound 232 Methyl 2- 3,4-Dimethoxy- 6-Methoxy-2- aminobenzoate benzoyl chloride naphthaldehyde Compound 233 Methyl 2-amino- 3,4-Dimethoxy- 4-Biphenyl- benzoate benzoyl chloride carboxaldehyde Compound 234 Methyl 2- 3,4-Dimethoxy- 4-Bromo- aminobenzoate benzoyl chloride benzaldehyde Compound 235 Methyl 2-amino- Benzoyl chloride Trans- benzoate cinnamaldehyde Compound 236 Methyl 2- 2-Fluorobenzoyl 2-Fluoro- aminobenzoate chloride benzaldehyde Compound 237 Methyl 2- 2-Fluorobenzoyl 3-Fluoro- aminobenzoate chloride benzaldehyde Compound 238 Methyl 2- 2-Fluorobenzoyl m-Tolualdehyde aminobenzoate chloride Compound 239 Methyl 2-amino- 2-Fluorobenzoyl 2-Hydroxy-3-tert- benzoate chloride butylbenzaldehyde Compound 240 Methyl 2- 3,4-Dimethoxy- 4-Nitrobenzaldehyde aminobenzoate benzoyl chloride Compound 241 Methyl 2-amino- 3,4-Dimethoxy- 4-Diethylamino- benzoate benzoyl chloride benzaldehyde Compound 242 Methyl 2-amino-5- 3,5-Dimethoxy- 3-Fluoro- hydroxybenzoate benzoyl chloride benzaldehyde Compound 243 Methyl 2-amino-5- 3,4-Dimethoxy- 2-Pyridyl- bromobenzoate benzoyl chloride carboxaldehyde Compound 244 Methyl 2-amino-5- 3,4-Dimethoxy- 2-Pyridyl- chlorobenzoate benzoyl chloride carboxaldehyde Compound 245 Methyl 2-amino- 3,4-Dimethoxy- 2-Pyridyl- benzoate benzoyl chloride carboxaldehyde Compound 246 Methyl 2-amino-5- 3,4-Dimethoxy- 6-Methyl-2- chlorobenzoate benzoyl chloride pyridine- carboxaldehyde Compound 247 Methyl 2- 3,4-Dimethoxy- 6-Methyl-2- aminobenzoate benzoyl chloride pyridine- carboxaldehyde Compound 248 Methyl 2-amino-5- 4-tert-butylbenzoyl m-Tolualdehyde bromobenzoate chloride Compound 249 Methyl 2- Isonicotinoyl 3-Methylaceto- aminobenzoate chloride phenone hydrochloride Compound 250 Methyl 2-amino-5- Nicotinoyl chloride 3-Methylaceto- chlorobenzoate hydrochloride phenone Compound 251 Methyl 2- Nicotinoyl chloride 4-Methylaceto- aminobenzoate hydrochloride phenone Compound 252 Methyl 2-amino-5- Nicotinoyl chloride p-Tolualdehyde bromobenzoate hydrochloride Compound 253 Methyl 2- Isonicotinoyl m-Tolualdehyde aminobenzoate chloride hydrochloride Vacant number Compound 255 Methyl 2-amino-5- 4-(Chloromethyl)- 3-Fluorobenzaldehyde 4-Mercapto- bromobenzoate benzoyl chloride pyridine Compound 256 Methyl 2-amino-5- 4-(Chloromethyl)- 4-Fluorobenzaldehyde 4-Mercapto- bromobenzoate benzoyl chloride pyridine Compound 257 Methyl 2-amino-5- 4-(Chloromethyl)- m-Tolualdehyde 4-Mercapto- bromobenzoate benzoyl chloride pyridine Compound 258 Methyl 2-amino-5- 4-(Chloromethyl)- p-Tolualdehyde 4-Mercapto- bromobenzoate benzoyl chloride pyridine Compound 259 Methyl 2-amino-5- 4-(Chloromethyl)- 3,4-Dimethyl- 4-Mercapto- bromobenzoate benzoyl chloride benzaldehyde pyridine Compound 260 Methyl 2-amino-5- 4-(Chloromethyl)- 4-Chloro-3-tri- 4-Mercapto- bromobenzoate benzoyl chloride fluoromethyl- pyridine benzaldehyde Compound 261 Methyl 2-amino-5- 4-(Chloromethyl)- 3-Fluorobenzaldehyde 2-Mercapto- bromobenzoate benzoyl chloride ethanol Compound 262 Methyl 2-amino-5- 4-(Chloromethyl)- 4-Fluorobenzaldehyde 2-Mercapto- bromobenzoate benzoyl chloride ethanol Compound 263 Methyl 2-amino-5- 4-(Chloromethyl)- m-Tolualdehyde 2-Mercapto- bromobenzoate benzoyl chloride ethanol Compound 264 Methyl 2-amino-5- 4-(Chloromethyl)- p-Tolualdehyde 2-Mercapto- bromobenzoate benzoyl chloride ethanol Compound 265 Methyl 2-amino-5- 4-(Chloromethyl)- 3,4-Dimethyl- 2-Mercapto- bromobenzoate benzoyl chloride benzaldehyde ethanol Compound 266 Methyl 2-amino-5- 4-(Chloromethyl)- 4-Chloro-3-tri- 2-Mercapto- bromobenzoate benzoyl chloride fluoromethyl- ethanol benzaldehyde Compound 267 Methyl 2-amino-5- 3-(Chloromethyl)- 3,4-Dimethyl- 3-Mercapto- bromobenzoate benzoyl chloride benzaldehyde 1,2,4-triazole Compound 268 Methyl 2-amino-5- 3-(Chloromethyl)- p-Tolualdehyde 3-Mercapto- bromobenzoate benzoyl chloride 1,2,4-triazole Compound 269 Methyl 2-amino-5- 3-(Chloromethyl)- m-Tolualdehyde 3-Mercapto- bromobenzoate benzoyl chloride 1,2,4-triazole Compound 270 Methyl 2-amino-5- 3-(Chloromethyl)- 4-Fluorobenzaldehyde 3-Mercapto- bromobenzoate benzoyl chloride 1,2,4-triazole Compound 271 Methyl 2-amino-5- 3-(Chloromethyl)- 3-Fluorobenzaldehyde 3-Mercapto- bromobenzoate benzoyl chloride 1,2,4-triazole Compound 272 Methyl 2-amino-5- 3-(Chloromethyl)- 4-Chloro-3-tri- 3-Mercapto- bromobenzoate benzoyl chloride fluoromethyl- 1,2,4-triazole benzaldehyde Compound 273 Methyl 2-amino-5- 4-(Chloromethyl)- 3,4-Dimethyl- 3-Mercapto-1- bromobenzoate benzoyl chloride benzaldehyde propanol Compound 274 Methyl 2-amino-5- 4-(Chloromethyl)- p-Tolualdehyde 3-Mercapto-1- bromobenzoate benzoyl chloride propanol Compound 275 Methyl 2-amino-5- 4-(Chloromethyl)- m-Tolualdehyde 3-Mercapto-1- bromobenzoate benzoyl chloride propanol Compound 276 Methyl 2-amino-5- 4-(Chloromethyl)- 4-Fluorobenzaldehyde 3-Mercapto-1- bromobenzoate benzoyl chloride propanol Compound 277 Methyl 2-amino-5- 4-(Chloromethyl)- 3-Fluorobenzaldehyde 3-Mercapto-1- bromobenzoate benzoyl chloride propanol Compound 278 Methyl 2-amino-5- 4-(Chloromethyl)- 4-Chloro-3-tri- 3-Mercapto-1- bromobenzoate benzoyl chloride fluoromethyl- propanol benzaldehyde Compound 279 Methyl 2-amino-5- 3-(Chloromethyl)- 3,4-Dimethyl- 4-(2-Amino- bromobenzoate benzoyl chloride benzaldehyde ethyl)- morpholine Compound 280 Methyl 2-amino-5- 4-(Chloromethyl)- 3,4-Dimethyl- N,N-Diethyl- bromobenzoate benzoyl chloride benzaldehyde N′-methyl- ethylene- diamine Compound 281 Methyl 2-amino-5- 4-(Chloromethyl)- 3,4-Dimethyl- 4-(2-Amino- bromobenzoate benzoyl chloride benzaldehyde ethyl)- morpholine Compound 282 Methyl 2-amino-5- 4-(Chloromethyl)- p-Tolualdehyde 4-(2-Amino- bromobenzoate benzoyl chloride ethyl)- morpholine Compound 283 Methyl 2-amino-5- 4-(Chloromethyl)- m-Tolualdehyde 4-(2-Amino- bromobenzoate benzoyl chloride ethyl)- morpholine Compound 284 Methyl 2-amino-5- 4-(Chloromethyl)- 4-Fluorobenzaldehyde 4-(2-Amino- bromobenzoate benzoyl chloride ethyl)- morpholine Compound 285 Methyl 2-amino-5- 4-(Chloromethyl)- p-Tolualdehyde N,N-Diethyl- bromobenzoate benzoyl chloride N′-methyl- ethylene- diamine Compound 286 Methyl 2-amino-5- 4-(Chloromethyl)- m-Tolualdehyde N,N-Diethyl- bromobenzoate benzoyl chloride N′-methyl- ethylene- diamine Compound 287 Methyl 2-amino-5- 4-(Chloromethyl)- 4-Fluorobenzaldehyde N,N-Diethyl- bromobenzoate benzoyl chloride N′-methyl- ethylene- diamine Compound 288 Methyl 2-amino-5- 4-(Chloromethyl)- 3-Fluorobenzaldehyde N,N-Diethyl- bromobenzoate benzoyl chloride N′-methyl- ethylene- diamine Compound 289 Methyl 2-amino-5- 4-(Chloromethyl)- 4-Chloro-3-tri- N,N-Diethyl- bromobenzoate benzoyl chloride fluoromethyl- N′-methyl- benzaldehyde ethylene- diamine Compound 290 Methyl 2-amino-5- 4-(Chloromethyl)- p-Methoxy N,N-Diethyl- bromobenzoate benzoyl chloride benzaldehyde N′-methyl- ethylene- diamine Compound 291 Methyl 2-amino-5- 4-(Chloromethyl)- m-Methoxy- N,N-Diethyl- bromobenzoate benzoyl chloride benzaldehyde N′-methyl- ethylene- diamine Compound 292 Methyl 2-amino-5- 4-(Chloromethyl)- 3,4-Dimethyl- N,N-Diethyl- bromobenzoate benzoyl chloride benzaldehyde ethylene- diamine Compound 293 Methyl 2-amino-5- 4-(Chloromethyl)- p-Tolualdehyde N,N-Diethyl- bromobenzoate benzoyl chloride ethylene- diamine Compound 294 Methyl 2-amino-5- 4-(Chloromethyl)- m-Tolualdehyde N,N-Diethyl- bromobenzoate benzoyl chloride ethylene- diamine Compound 295 Methyl 2-amino-5- 4-(Chloromethyl)- 4-Fluorobenzaldehyde N,N-Diethyl- bromobenzoate benzoyl chloride ethylene- diamine Compound 296 Methyl 2-amino-5- 4-(Chloromethyl)- 3-Fluorobenzaldehyde N,N-Diethyl- bromobenzoate benzoyl chloride ethylene- diamine Compound 297 Methyl 2-amino-5- 4-(Chloromethyl)- 4-Chloro-3-tri- N,N-Diethyl- bromobenzoate benzoyl chloride fluoromethyl- ethylene- benzaldehyde diamine Compound 298 Methyl 2-amino-5- 4-(Chloromethyl)- p-Methoxy- N,N-Diethyl- bromobenzoate benzoyl chloride benzaldehyde ethylene- diamine Compound 299 Methyl 2-amino-5- 4-(Chloromethyl)- m-Methoxy- N,N-Diethyl- bromobenzoate benzoyl chloride benzaldehyde ethylene- diamine Compound 300 Methyl 2-amino-5- 4-(Chloromethyl)- 3,4-Dimethyl- N-(3-Amino- bromobenzoate benzoyl chloride benzaldehyde propyl)di- ethanolamine Compound 301 Methyl 2-amino-5- 4-(Chloromethyl)- 3-Fluorobenzaldehyde N-(3-Amino- bromobenzoate benzoyl chloride propyl)di- ethanolamine Compound 302 Methyl 2-amino-5- 4-(Chloromethyl)- 4-Chloro-3-tri- N-(3-Amino- bromobenzoate benzoyl chloride fluoromethyl- propyl)di- benzaldehyde ethanolamine Compound 303 Methyl 2-amino-5- 4-(Chloromethyl)- 3,4-Dimethyl- Diisopropanol- bromobenzoate benzoyl chloride benzaldehyde amine Compound 304 Methyl 2-amino-5- 4-(Chloromethyl)- p-Tolualdehyde Diisopropanol- bromobenzoate benzoyl chloride amine Compound 305 Methyl 2-amino-5- 4-(Chloromethyl)- 3,4-Dimethyl- N-(2-(1- bromobenzoate benzoyl chloride benzaldehyde Piperazino)- acetyl)- morpholine Compound 306 Methyl 2-amino-5- 4-(Chloromethyl)- 4-Chloro-3-tri- N-(2-(1- bromobenzoate benzoyl chloride fluoromethyl- Piperazino)- benzaldehyde acetyl)- morpholine Compound 307 Methyl 2-amino-5- 4-(Chloromethyl)- p-Methoxy- N-(2-(1- bromobenzoate benzoyl chloride benzaldehyde Piperazino)- acetyl)- morpholine Compound 308 Methyl 2-amino-5- 4-(Chloromethyl)- 3,4-Dimethyl- 4-Piperidino- bromobenzoate benzoyl chloride benzaldehyde piperidine Compound 309 Methyl 2-amino-5- 4-(Chloromethyl)- p-Tolualdehyde 4-Piperidino- bromobenzoate benzoyl chloride piperidine Compound 310 Methyl 2-amino-5- 4-(Chloromethyl)- m-Tolualdehyde 4-Piperidino- bromobenzoate benzoyl chloride piperidine Compound 311 Methyl 2-amino-5- 4-(Chloromethyl)- 4-Fluorobenzaldehyde 4-Piperidino- bromobenzoate benzoyl chloride piperidine Compound 312 Methyl 2-amino-5- 4-(Chloromethyl)- 3-Fluorobenzaldehyde 4-Piperidino- bromobenzoate benzoyl chloride piperidine Compound 313 Methyl 2-amino-5- 4-(Chloromethyl)- 4-Chloro-3-tri- 4-Piperidino- bromobenzoate benzoyl chloride fluoromethyl- piperidine benzaldehyde Compound 314 Methyl 2-amino-5- 4-(Chloromethyl)- p-Methoxy- 4-Piperidino- bromobenzoate benzoyl chloride benzaldehyde piperidine Compound 315 Methyl 2-amino-5- 4-(Chloromethyl)- m-Methoxy- 4-Piperidino- bromobenzoate benzoyl chloride benzaldehyde piperidine Compound 316 Methyl 2-amino-5- 4-(Chloromethyl)- 3,4-Dimethyl- 1-(2-Hydroxy- bromobenzoate benzoyl chloride benzaldehyde ethyl)- piperazine Compound 317 Methyl 2-amino-5- 4-(Chloromethyl)- p-Tolualdehyde 1-(2-Hydroxy- bromobenzoate benzoyl chloride ethyl)- piperazine Compound 318 Methyl 2-amino-5- 4-(Chloromethyl)- m-Tolualdehyde 1-(2-Hydroxy- bromobenzoate benzoyl chloride ethyl)- piperazine Compound 319 Methyl 2-amino-5- 4-(Chloromethyl)- 4-Fluorobenzaldehyde 1-(2-Hydroxy- bromobenzoate benzoyl chloride ethyl)- piperazine Compound 320 Methyl 2-amino-5- 4-(Chloromethyl)- 3-Fluorobenzaldehyde 1-(2-Hydroxy- bromobenzoate benzoyl chloride ethyl)- piperazine Compound 321 Methyl 2-amino-5- 4-(Chloromethyl)- 4-Chloro-3-tri- 1-(2-Hydroxy- bromobenzoate benzoyl chloride fluoromethyl- ethyl)- benzaldehyde piperazine Compound 322 Methyl 2-amino-5- 4-(Chloromethyl)- p-Methoxy- 1-(2-Hydroxy- bromobenzoate benzoyl chloride benzaldehyde ethyl)- piperazine Compound 323 Methyl 2-amino-5- 4-(Chloromethyl)- m-Methoxy- 1-(2-Hydroxy- bromobenzoate benzoyl chloride benzaldehyde ethyl)- piperazine Compound 324 Methyl 2-amino-5- 4-(Chloromethyl)- 3,4-Dimethyl- 4-Hydroxy- bromobenzoate benzoyl chloride benzaldehyde piperidine Compound 325 Methyl 2-amino-5- 4-(Chloromethyl)- p-Tolualdehyde 4-Hydroxy- bromobenzoate benzoyl chloride piperidine Compound 326 Methyl 2-amino-5- 4-(Chloromethyl)- m-Tolualdehyde 4-Hydroxy- bromobenzoate benzoyl chloride piperidine Compound 327 Methyl 2-amino-5- 4-(Chloromethyl)- 4-Fluorobenzaldehyde 4-Hydroxy- bromobenzoate benzoyl chloride piperidine Compound 328 Methyl 2-amino-5- 4-(Chloromethyl)- 3-Fluorobenzaldehyde 4-Hydroxy- bromobenzoate benzoyl chloride piperidine Compound 329 Methyl 2-amino-5- 4-(Chloromethyl)- 4-Chloro-3-tri- 4-Hydroxy- bromobenzoate benzoyl chloride fluoromethyl- piperidine benzaldehyde Compound 330 Methyl 2-amino-5- 4-(Chloromethyl)- p-Methoxybenzaldehyde 4-Hydroxy- bromobenzoate benzoyl chloride piperidine Compound 331 Methyl 2-amino-5- 4-(Chloromethyl)- m-Methoxybenzaldehyde 4-Hydroxy- bromobenzoate benzoyl chloride piperidine Compound 332 Methyl 2-amino-5- 4-(Chloromethyl)- 3,4-Dimethyl- 4-Piperidine- bromobenzoate benzoyl chloride benzaldehyde methanol Compound 333 Methyl 2-amino-5- 4-(Chloromethyl)- p-Tolualdehyde 4-Piperidine- bromobenzoate benzoyl chloride methanol Compound 334 Methyl 2-amino-5- 4-(Chloromethyl)- m-Tolualdehyde 4-Piperidine- bromobenzoate benzoyl chloride methanol Compound 335 Methyl 2-amino-5- 4-(Chloromethyl)- 4-Fluorobenzaldehyde 4-Piperidine- bromobenzoate benzoyl chloride methanol Compound 336 Methyl 2-amino-5- 4-(Chloromethyl)- 3-Fluorobenzaldehyde 4-Piperidine- bromobenzoate benzoyl chloride methanol Compound 337 Methyl 2-amino-5- 4-(Chloromethyl)- 4-Chloro-3-tri- 4-Piperidine- bromobenzoate benzoyl chloride fluoromethyl- methanol benzaldehyde Compound 338 Methyl 2-amino-5- 4-(Chloromethyl)- p-Methoxy- 4-Piperidine- bromobenzoate benzoyl chloride benzaldehyde methanol Compound 339 Methyl 2-amino-5- 4-(Chloromethyl)- m-Methoxy- 4-Piperidine- bromobenzoate benzoyl chloride benzaldehyde methanol Compound 340 Methyl 2-amino-5- 4-(Chloromethyl)- 3,4-Dimethyl- 4-Piperidine- bromobenzoate benzoyl chloride benzaldehyde ethanol Compound 341 Methyl 2-amino-5- 3-(Chloromethyl)- 3-Fluorobenzaldehyde 3-Mercapto- bromobenzoate benzoyl chloride 1,2,4-triazole Compound 342 Methyl 3-amino-4- 3-(Chloromethyl)- 3,4-Dimethyl- N,N-Diethyl- methylthiophene-2- benzoyl chloride benzaldehyde N′-methyl- carboxylate ethylene- diamine Compound 343 Methyl 3-amino-4- 3-(Chloromethyl)- p-Tolualdehyde N,N-Diethyl- methylthiophene-2- benzoyl chloride N′-methyl- carboxylate ethylene- diamine Compound 344 Methyl 3-amino-4- 3-(Chloromethyl)- 4-Chloro-3-tri- N,N-Diethyl- methylthiophene-2- benzoyl chloride fluoromethyl- N′-methyl- carboxylate benzaldehyde ethylene- diamine Compound 345 Methyl 3-amino-4- 3-(Chloromethyl)- 3,4-Dimethyl- 4-Piperidino- methylthiophene-2- benzoyl chloride benzaldehyde piperidine carboxylate Compound 346 Methyl 2-amino-5- Nicotinoyl chloride Trans- bromobenzoate hydrochloride cinnamaldehyde Compound 347 Methyl 2-amino-5- Isonicotinoyl Trans- bromobenzoate chloride cinnamaldehyde hydrochloride Compound 348 Methyl 2-amino-5- Nicotinoyl chloride Trans- chlorobenzoate hydrochloride cinnamaldehyde Compound 349 Methyl 2-amino-5- Isonicotinoyl Trans- chlorobenzoate chloride cinnamaldehyde hydrochloride Compound 350 Methyl 2-amino-5- Isonicotinoyl 3-(2-Hydroxy- bromobenzoate chloride ethoxy)- hydrochloride benzaldehyde Compound 351 Methyl 2-amino-5- Isonicotinoyl 3-(2-Hydroxy- chlorobenzoate chloride ethoxy)- hydrochloride benzaldehyde Compound 352 Methyl 2-amino-5- Nicotinoyl chloride 2-Methoxy- bromobenzoate hydrochloride cinnamaldehyde Compound 353 Methyl 2-amino-5- Isonicotinoyl 2-Methoxy- bromobenzoate chloride cinnamaldehyde hydrochloride Compound 354 Methyl 2-amino-5- Nicotinoyl chloride 2-Methoxy- chlorobenzoate hydrochloride cinnamaldehyde Compound 355 Methyl 2-amino-5- Isonicotinoyl 2-Methoxy- chlorobenzoate chloride cinnamaldehyde hydrochloride Compound 356 Methyl 2-amino-5- Picolinoyl chloride p-Tolualdehyde bromobenzoate hydrochloride Compound 357 Methyl 2-amino-5- 4-(Chloromethyl)- m-Tolualdehyde 3-Fluoro- bromobenzoate benzoyl chloride benzenethiol Compound 358 Methyl 2- Nicotinoyl chloride 4-Dimethyl- aminobenzoate hydrochloride amino- cinnamaldehyde Compound 359 Methyl 2-amino-5- Picolinoyl chloride 3-Fluorobenzaldehyde chlorobenzoate hydrochloride Compound 360 Methyl 2-amino-5- Picolinoyl chloride 4-Fluorobenzaldehyde chlorobenzoate hydrochloride Compound 361 Methyl 2-amino-5- Picolinoyl chloride m-Tolualdehyde chlorobenzoate hydrochloride Compound 362 Methyl 2-amino-5- Picolinoyl chloride p-Tolualdehyde chlorobenzoate hydrochloride Compound 363 Methyl 2-amino-5- Picolinoyl chloride 3,4-Dimethyl- chlorobenzoate hydrochloride benzaldehyde Compound 364 Methyl 2-amino-5- Picolinoyl chloride 4-Chloro-3-tri- chlorobenzoate hydrochloride fluoromethyl- benzaldehyde Vacant number Compound 366 Methyl 2-amino-5- 3-(Chloromethyl)- 3,4-Dimethyl- 4-Mercapto- chlorobenzoate benzoyl chloride benzaldehyde pyridine Compound 367 Methyl 2-amino-5- 3,4-Dimethoxy- p-Tolualdehyde bromobenzoate benzoyl chloride Compound 368 Methyl 2-amino-5- 3-(Chloromethyl)- 3-Fluorobenzaldehyde 4-Piperidino- chlorobenzoate benzoyl chloride piperidine Compound 369 Methyl 2-amino-5- 3-(Chloromethyl)- 4-Fluorobenzaldehyde 4-Piperidino- chlorobenzoate benzoyl chloride piperidine Compound 370 Methyl 2-amino-5- 3-(Chloromethyl)- m-Tolualdehyde 4-Piperidino- chlorobenzoate benzoyl chloride piperidine Compound 371 Methyl 2-amino-5- 3-(Chloromethyl)- p-Tolualdehyde 4-Piperidino- chlorobenzoate benzoyl chloride piperidine Compound 372 Methyl 2-amino-5- 3-(Chloromethyl)- 3,4-Dimethyl- 4-Piperidino- chlorobenzoate benzoyl chloride benzaldehyde piperidine Compound 373 Methyl 2-amino-5- 3-(Chloromethyl)- 4-Chloro-3-tri- 4-Piperidino- chlorobenzoate benzoyl chloride fluoromethyl- piperidine benzaldehyde Compound 374 Methyl 2-amino-5- 3-(Chloromethyl)- 3-Methoxy- 4-Piperidino- chlorobenzoate benzoyl chloride benzaldehyde piperidine Compound 375 Methyl 2-amino-5- 3-(Chloromethyl)- 4-Methoxy- 4-Piperidino- chlorobenzoate benzoyl chloride benzaldehyde piperidine Compound 376 Methyl 2-amino-5- 3-(Chloromethyl)- 3-Hydroxy- 4-Piperidino- chlorobenzoate benzoyl chloride benzaldehyde piperidine Compound 377 Methyl 2-amino-5- 3-(Chloromethyl)- 4-Hydroxy- 4-Piperidino- chlorobenzoate benzoyl chloride benzaldehyde piperidine Compound 378 Methyl 2-amino-5- 4-(Chloromethyl)- 3-Methoxy- 4-Piperidino- bromobenzoate benzoyl chloride benzaldehyde piperidine Compound 379 Methyl 2-amino-5- 3-(Chloromethyl)- 3-Fluorobenzaldehyde N,N-Diethyl- chlorobenzoate benzoyl chloride N′-methyl- ethylene- diamine Compound 380 Methyl 2-amino-5- 3-(Chloromethyl)- 4-Fluorobenzaldehyde N,N-Diethyl- chlorobenzoate benzoyl chloride N′-methyl- ethylene- diamine Compound 381 Methyl 2-amino-5- 3-(Chloromethyl)- m-Tolualdehyde N,N-Diethyl- chlorobenzoate benzoyl chloride N′-methyl- ethylene- diamine Compound 382 Methyl 2-amino-5- 3-(Chloromethyl)- p-Tolualdehyde N,N-Diethyl- chlorobenzoate benzoyl chloride N′-methyl- ethylene- diamine Compound 383 Methyl 2-amino-5- 3-(Chloromethyl)- 3,4-Dimethyl- N,N-Diethyl- chlorobenzoate benzoyl chloride benzaldehyde N′-methyl- ethylene- diamine Compound 384 Methyl 2-amino-5- 3-(Chloromethyl)- 4-Chloro-3-tri- N,N-Diethyl- chlorobenzoate benzoyl chloride fluoromethyl- N′-methyl- benzaldehyde ethylene- diamine Compound 385 Methyl 2-amino-5- 3-(Chloromethyl)- 3-Methoxy- N,N-Diethyl- chlorobenzoate benzoyl chloride benzaldehyde N′-methyl- ethylene- diamine Compound 386 Methyl 2-amino-5- 3-(Chloromethyl)- 4-Methoxy- N,N-Diethyl- chlorobenzoate benzoyl chloride benzaldehyde N′-methyl- ethylene- diamine Compound 387 Methyl 2-amino-5- 3-(Chloromethyl)- 3-Hydroxy- N,N-Diethyl- chlorobenzoate benzoyl chloride benzaldehyde N′-methyl- ethylene- diamine Compound 388 Methyl 2-amino-5- 3-(Chloromethyl)- 4-Hydroxy- N,N-Diethyl- chlorobenzoate benzoyl chloride benzaldehyde N′-methyl- ethylene- diamine Compound 389 Methyl 2-amino-5- 3-(Chloromethyl)- 3-Fluorobenzaldehyde 3-Mercapto- chlorobenzoate benzoyl chloride 1,2,4-triazole Compound 390 Methyl 2-amino-5- 3-(Chloromethyl)- 4-Fluorobenzaldehyde 3-Mercapto- chlorobenzoate benzoyl chloride 1,2,4-triazole Compound 391 Methyl 2-amino-5- 3-(Chloromethyl)- m-Tolualdehyde 3-Mercapto- chlorobenzoate benzoyl chloride 1,2,4-triazole Compound 392 Methyl 2-amino-5- 3-(Chloromethyl)- p-Tolualdehyde 3-Mercapto- chlorobenzoate benzoyl chloride 1,2,4-triazole Compound 393 Methyl 2-amino-5- 3-(Chloromethyl)- 4-Chloro-3-tri- 3-Mercapto- chlorobenzoate benzoyl chloride fluoromethyl- 1,2,4-triazole benzaldehyde Compound 394 Methyl 2-amino-5- 3-(Chloromethyl)- 3-Fluorobenzaldehyde 2-(Methyl- chlorobenzoate benzoyl chloride amino)ethanol Compound 395 Methyl 2-amino-5- 3-(Chloromethyl)- 4-Fluorobenzaldehyde 2-(Methyl- chlorobenzoate benzoyl chloride amino)ethanol Compound 396 Methyl 2-amino-5- 3-(Chloromethyl)- m-Tolualdehyde 2-(Methyl- chlorobenzoate benzoyl chloride amino)ethanol Compound 397 Methyl 2-amino-5- 3-(Chloromethyl)- p-Tolualdehyde 2-(Methyl- chlorobenzoate benzoyl chloride amino)ethanol Compound 398 Methyl 2-amino-5- 3-(Chloromethyl)- 3,4-Dimethyl- 2-(Methyl- chlorobenzoate benzoyl chloride benzaldehyde amino)ethanol Compound 399 Methyl 2-amino-5- 3-(Chloromethyl)- 4-Chloro-3-tri- 2-(Methyl- chlorobenzoate benzoyl chloride fluoromethyl- amino)ethanol benzaldehyde Compound 400 Methyl 2-amino-5- 3-(Chloromethyl)- 3-Methoxy- 2-(Methyl- chlorobenzoate benzoyl chloride benzaldehyde amino)ethanol Compound 401 Methyl 2-amino-5- 3-(Chloromethyl)- 4-Methoxy- 2-(Methyl- chlorobenzoate benzoyl chloride benzaldehyde amino)ethanol Compound 402 Methyl 2-amino-5- 3-(Chloromethyl)- 3-Hydroxy- 2-(Methyl- chlorobenzoate benzoyl chloride benzaldehyde amino)ethanol Compound 403 Methyl 2-amino-5- 3-(Chloromethyl)- 4-Hydroxy- 2-(Methyl- chlorobenzoate benzoyl chloride benzaldehyde amino)ethanol Compound 404 Methyl 2-amino-5- 3-(Chloromethyl)- m-Tolualdehyde Diethanol- chlorobenzoate benzoyl chloride amine Compound 405 Methyl 2-amino-5- 3-(Chloromethyl)- p-Tolualdehyde Diethanol- chlorobenzoate benzoyl chloride amine Compound 406 Methyl 2-amino-5- 3-(Chloromethyl)- 3,4-Dimethyl- Diethanol- chlorobenzoate benzoyl chloride benzaldehyde amine Compound 407 Methyl 2-amino-5- 3-(Chloromethyl)- 4-Chloro-3-tri- Diethanol- chlorobenzoate benzoyl chloride fluoromethyl- amine benzaldehyde Compound 408 Methyl 2-amino-5- 3-(Chloromethyl)- 3-Methoxy- Diethanol- chlorobenzoate benzoyl chloride benzaldehyde amine Compound 409 Methyl 2-amino-5- 3-(Chloromethyl)- 4-Methoxy- Diethanol- chlorobenzoate benzoyl chloride benzaldehyde amine Compound 410 Methyl 2-amino-5- 3-(Chloromethyl)- 3-Hydroxy- Diethanol- chlorobenzoate benzoyl chloride benzaldehyde amine Compound 411 Methyl 2-amino-5- 3-(Chloromethyl)- 4-Hydroxy- Diethanol- chlorobenzoate benzoyl chloride benzaldehyde amine Compound 412 Methyl 2-amino-5- 4-(Chloromethyl)- 3-Fluorobenzaldehyde 2-(Methyl- chlorobenzoate benzoyl chloride amino)ethanol Compound 413 Methyl 2-amino-5- 4-(Chloromethyl)- 4-Fluorobenzaldehyde 2-(Methyl- chlorobenzoate benzoyl chloride amino)ethanol Compound 414 Methyl 2-amino-5- 4-(Chloromethyl)- m-Tolualdehyde 2-(Methyl- chlorobenzoate benzoyl chloride amino)ethanol Compound 415 Methyl 2-amino-5- 4-(Chloromethyl)- p-Tolualdehyde 2-(Methyl- chlorobenzoate benzoyl chloride amino)ethanol Compound 416 Methyl 2-amino-5- 4-(Chloromethyl)- 3,4-Dimethyl- 2-(Methyl- chlorobenzoate benzoyl chloride benzaldehyde amino)ethanol Compound 417 Methyl 2-amino-5- 4-(Chloromethyl)- 4-Chloro-3-tri- 2-(Methyl- chlorobenzoate benzoyl chloride fluoromethyl- amino)ethanol benzaldehyde Compound 418 Methyl 2-amino-5- 4-(Chloromethyl)- 3-Methoxy- 2-(Methyl- chlorobenzoate benzoyl chloride benzaldehyde amino)ethanol Compound 419 Methyl 2-amino-5- 4-(Chloromethyl)- 4-Methoxy- 2-(Methyl- chlorobenzoate benzoyl chloride benzaldehyde amino)ethanol Compound 420 Methyl 2-amino-5- 4-(Chloromethyl)- 3-Hydroxy- 2-(Methyl- chlorobenzoate benzoyl chloride benzaldehyde amino)ethanol Compound 421 Methyl 2-amino-5- 4-(Chloromethyl)- 4-Hydroxy- 2-(Methyl- chlorobenzoate benzoyl chloride benzaldehyde amino)ethanol Compound 422 Methyl 2-amino-5- 3-(Chloromethyl)- 3-Fluorobenzaldehyde 2-(Ethyl- chlorobenzoate benzoyl chloride amino)ethanol Compound 423 Methyl 2-amino-5- 3-(Chloromethyl)- 4-Fluorobenzaldehyde 2-(Ethyl- chlorobenzoate benzoyl chloride amino)ethanol Compound 424 Methyl 2-amino-5- 3-(Chloromethyl)- m-Tolualdehyde 2-(Ethyl- chlorobenzoate benzoyl chloride amino)ethanol Compound 425 Methyl 2-amino-5- 3-(Chloromethyl)- p-Tolualdehyde 2-(Ethyl- chlorobenzoate benzoyl chloride amino)ethanol Compound 426 Methyl 2-amino-5- 3-(Chloromethyl)- 3,4-Dimethyl- 2-(Ethyl- chlorobenzoate benzoyl chloride benzaldehyde amino)ethanol Compound 427 Methyl 2-amino-5- 3-(Chloromethyl)- 4-Chloro-3-tri- 2-(Ethyl- chlorobenzoate benzoyl chloride fluoromethyl- amino)ethanol benzaldehyde Compound 428 Methyl 2-amino-5- 3-(Chloromethyl)- 3-Methoxy- 2-(Ethyl- chlorobenzoate benzoyl chloride benzaldehyde amino)ethanol Compound 429 Methyl 2-amino-5- 3-(Chloromethyl)- 4-Methoxy- 2-(Ethyl- chlorobenzoate benzoyl chloride benzaldehyde amino)ethanol Compound 430 Methyl 2-amino-5- 3-(Chloromethyl)- 3-Hydroxy- 2-(Ethyl- chlorobenzoate benzoyl chloride benzaldehyde amino)ethanol Compound 431 Methyl 2-amino-5- 3-(Chloromethyl)- 4-Hydroxy- 2-(Ethyl- chlorobenzoate benzoyl chloride benzaldehyde amino)ethanol Compound 432 Methyl 2-amino-5- 4-(Chloromethyl)- 3-Fluorobenzaldehyde 2-(Ethyl- chlorobenzoate benzoyl chloride amino)ethanol Compound 433 Methyl 2-amino-5- 4-(Chloromethyl)- 4-Fluorobenzaldehyde 2-(Ethyl- chlorobenzoate benzoyl chloride amino)ethanol Compound 434 Methyl 2-amino-5- 4-(Chloromethyl)- m-Tolualdehyde 2-(Ethyl- chlorobenzoate benzoyl chloride amino)ethanol Compound 435 Methyl 2-amino-5- 4-(Chloromethyl)- p-Tolualdehyde 2-(Ethyl- chlorobenzoate benzoyl chloride amino)ethanol Compound 436 Methyl 2-amino-5- 4-(Chloromethyl)- 3,4-Dimethyl- 2-(Ethyl- chlorobenzoate benzoyl chloride benzaldehyde amino)ethanol Compound 437 Methyl 2-amino-5- 4-(Chloromethyl)- 4-Chloro-3- 2-(Ethyl- chlorobenzoate benzoyl chloride trifluoromethyl amino)ethanol benzaldehyde Compound 438 Methyl 2-amino-5- 4-(Chloromethyl)- 3-Methoxy- 2-(Ethyl- chlorobenzoate benzoyl chloride benzaldehyde amino)ethanol Compound 439 Methyl 2-amino-5- 4-(Chloromethyl)- 4-Methoxy- 2-(Ethyl- chlorobenzoate benzoyl chloride benzaldehyde amino)ethanol Compound 440 Methyl 2-amino-5- 4-(Chloromethyl)- 3-Hydroxy- 2-(Ethyl- chlorobenzoate benzoyl chloride benzaldehyde amino)ethanol Compound 441 Methyl 2-amino-5- 4-(Chloromethyl)- 4-Hydroxy- 2-(Ethyl- chlorobenzoate benzoyl chloride benzaldehyde amino)ethanol Compound 442 Methyl 2-amino-5- 4-(Chloromethyl)- 3-Fluorobenzaldehyde 2-Diethyl- chlorobenzoate benzoyl chloride amino- ethanethiol hydrochloride Compound 443 Methyl 2-amino-5- 4-(Chloromethyl)- 4-Fluorobenzaldehyde 2-Diethyl- chlorobenzoate benzoyl chloride amino- ethanethiol hydrochloride Compound 444 Methyl 2-amino-5- 4-(Chloromethyl)- m-Tolualdehyde 2-Diethyl- chlorobenzoate benzoyl chloride amino- ethanethiol hydrochloride Compound 445 Methyl 2-amino-5- 4-(Chloromethyl)- p-Tolualdehyde 2-Diethyl- chlorobenzoate benzoyl chloride amino- ethanethiol hydrochloride Compound 446 Methyl 2-amino-5- 4-(Chloromethyl)- 3,4-Dimethyl- 2-Diethyl- chlorobenzoate benzoyl chloride benzaldehyde amino- ethanethiol hydrochloride Compound 447 Methyl 2-amino-5- 4-(Chloromethyl)- 4-Chloro-3-tri- 2-Diethyl- chlorobenzoate benzoyl chloride fluoromethyl- amino- benzaldehyde ethanethiol hydrochloride Compound 448 Methyl 2-amino-5- 4-(Chloromethyl)- 3-Methoxy- 2-Diethyl- chlorobenzoate benzoyl chloride benzaldehyde amino- ethanethiol hydrochloride Compound 449 Methyl 2-amino-5- 4-(Chloromethyl)- 4-Methoxy- 2-Diethyl- chlorobenzoate benzoyl chloride benzaldehyde amino- ethanethiol hydrochloride Compound 450 Methyl 2-amino-5- 4-(Chloromethyl)- 3-Hydroxy- 2-Diethyl- chlorobenzoate benzoyl chloride benzaldehyde amino- ethanethiol hydrochloride Compound 451 Methyl 2-amino-5- 4-(Chloromethyl)- 4-Hydroxy- 2-Diethyl- chlorobenzoate benzoyl chloride benzaldehyde amino- ethanethiol hydrochloride Compound 452 Methyl 2-amino-5- 3-(Chloromethyl)- 3-Fluorobenzaldehyde 2-Diethyl- chlorobenzoate benzoyl chloride amino- ethanethiol hydrochloride Compound 453 Methyl 2-amino-5- 3-(Chloromethyl)- 4-Fluorobenzaldehyde 2-Diethyl- chlorobenzoate benzoyl chloride amino- ethanethiol hydrochloride Compound 454 Methyl 2-amino-5- 3-(Chloromethyl)- m-Tolualdehyde 2-Diethyl- chlorobenzoate benzoyl chloride amino- ethanethiol hydrochloride Compound 455 Methyl 2-amino-5- 3-(Chloromethyl)- p-Tolualdehyde 2-Diethyl- chlorobenzoate benzoyl chloride amino- ethanethiol hydrochloride Compound 456 Methyl 2-amino-5- 3-(Chloromethyl)- 3,4-Dimethyl- 2-Diethyl- chlorobenzoate benzoyl chloride benzaldehyde amino- ethanethiol hydrochloride Compound 457 Methyl 2-amino-5- 3-(Chloromethyl)- 4-Chloro-3- 2-Diethyl- chlorobenzoate benzoyl chloride trifluoromethyl amino- benzaldehyde ethanethiol hydrochloride Compound 458 Methyl 2-amino-5- 3-(Chloromethyl)- 3-Methoxy- 2-Diethyl- chlorobenzoate benzoyl chloride benzaldehyde amino- ethanethiol hydrochloride Compound 459 Methyl 2-amino-5- 3-(Chloromethyl)- 4-Methoxy- 2-Diethyl- chlorobenzoate benzoyl chloride benzaldehyde amino- ethanethiol hydrochloride Compound 460 Methyl 2-amino-5- 3-(Chloromethyl)- 3-Hydroxy- 2-Diethyl- chlorobenzoate benzoyl chloride benzaldehyde amino- ethanethiol hydrochloride Compound 461 Methyl 2-amino-5- 3-(Chloromethyl)- 4-Hydroxy- 2-Diethyl- chlorobenzoate benzoyl chloride benzaldehyde amino- ethanethiol hydrochloride Compound 462 Methyl 2-amino-5- 3-(Chloromethyl)- 3-Fluoro- 1-(2-Dimethyl- chlorobenzoate benzoyl chloride benzaldehyde aminoethyl)- 5-mercapto- tetrazole Compound 463 Methyl 2-amino-5- 3-(Chloromethyl)- 4-Fluorobenzaldehyde 1-(2-Dimethyl- chlorobenzoate benzoyl chloride aminoethyl)- 5-mercapto- tetrazole Compound 464 Methyl 2-amino-5- 3-(Chloromethyl)- m-Tolualdehyde 1-(2-Dimethyl- chlorobenzoate benzoyl chloride aminoethyl)- 5-mercapto- tetrazole Compound 465 Methyl 2-amino-5- 3-(Chloromethyl)- p-Tolualdehyde 1-(2-Dimethyl- chlorobenzoate benzoyl chloride aminoethyl)- 5-mercapto- tetrazole Compound 466 Methyl 2-amino-5- 3-(Chloromethyl)- 3,4-Dimethyl- 1-(2-Dimethyl- chlorobenzoate benzoyl chloride benzaldehyde aminoethyl)- 5-mercapto- tetrazole Compound 467 Methyl 2-amino-5- 3-(Chloromethyl)- 4-Chloro-3-tri- 1-(2-Dimethyl- chlorobenzoate benzoyl chloride fluoromethyl- aminoethyl)- benzaldehyde 5-mercapto- tetrazole Compound 468 Methyl 2-amino-5- 3-(Chloromethyl)- 3-Methoxy- 1-(2-Dimethyl- chlorobenzoate benzoyl chloride benzaldehyde aminoethyl)- 5-mercapto- tetrazole Compound 469 Methyl 2-amino-5- 3-(Chloromethyl)- 4-Methoxy- 1-(2-Dimethyl- chlorobenzoate benzoyl chloride benzaldehyde aminoethyl)- 5-mercapto- tetrazole Compound 470 Methyl 2-amino-5- 3-(Chloromethyl)- 3-Hydroxy- 1-(2-Dimethyl- chlorobenzoate benzoyl chloride benzaldehyde aminoethyl)- 5-mercapto- tetrazole Compound 471 Methyl 2-amino-5- 3-(Chloromethyl)- 4-Hydroxy- 1-(2-Dimethyl- chlorobenzoate benzoyl chloride benzaldehyde aminoethyl)- 5-mercapto- tetrazole Compound 472 Methyl 2-amino-5- 3-(Chloromethyl)- 3-Fluorobenzaldehyde N,N-Diethyl- iodobenzoate benzoyl chloride N′-methyl- ethylene- diamine Compound 473 Methyl 2-amino-5- 3-(Chloromethyl)- 4-Fluorobenzaldehyde N,N-Diethyl- iodobenzoate benzoyl chloride N′-methyl- ethylene- diamine Compound 474 Methyl 2-amino-5- 3-(Chloromethyl)- m-Tolualdehyde N,N-Diethyl- iodobenzoate benzoyl chloride N′-methyl- ethylene- diamine Compound 475 Methyl 2-amino-5- 3-(Chloromethyl)- p-Tolualdehyde N,N-Diethyl- iodobenzoate benzoyl chloride N′-methyl- ethylene- diamine Compound 476 Methyl 2-amino-5- 3-(Chloromethyl)- 3,4-Dimethyl- N,N-Diethyl- iodobenzoate benzoyl chloride benzaldehyde N′-methyl- ethylene- diamine Compound 477 Methyl 2-amino-5- 3-(Chloromethyl)- 4-Chloro-3-tri- N,N-Diethyl- iodobenzoate benzoyl chloride fluoromethyl- N′-methyl- benzaldehyde ethylene- diamine Compound 478 Methyl 2-amino-5- 3-(Chloromethyl)- 3-Methoxy- N,N-Diethyl- iodobenzoate benzoyl chloride benzaldehyde N′-methyl- ethylene- diamine Compound 479 Methyl 2-amino-5- 3-(Chloromethyl)- 4-Methoxy- N,N-Diethyl- iodobenzoate benzoyl chloride benzaldehyde N′-methyl- ethylene- diamine Compound 480 Methyl 2-amino-5- 3-(Chloromethyl)- 3-Hydroxy- N,N-Diethyl- iodobenzoate benzoyl chloride benzaldehyde N′-methyl- ethylene- diamine Compound 481 Methyl 2-amino-5- 3-(Chloromethyl)- 4-Hydroxy- N,N-Diethyl- iodobenzoate benzoyl chloride benzaldehyde N′-methyl- ethylene- diamine Compound 482 Methyl 2-amino-5- 3-(Chloromethyl)- 3-Fluorobenzaldehyde 4-Piperidino- iodobenzoate benzoyl chloride piperidine Compound 483 Methyl 2-amino-5- 3-(Chloromethyl)- 3-Fluorobenzaldehyde 4-Piperidino- iodobenzoate benzoyl chloride piperidine Compound 484 Methyl 2-amino-5- 3-(Chloromethyl)- m-Tolualdehyde 4-Piperidino- iodobenzoate benzoyl chloride piperidine Compound 485 Methyl 2-amino-5- 3-(Chloromethyl)- p-Tolualdehyde 4-Piperidino- iodobenzoate benzoyl chloride piperidine Compound 486 Methyl 2-amino-5- 3-(Chloromethyl)- 3,4-Dimethyl- 4-Piperidino- iodobenzoate benzoyl chloride benzaldehyde piperidine Compound 487 Methyl 2-amino-5- 3-(Chloromethyl)- 4-Chloro-3-tri- 4-Piperidino- iodobenzoate benzoyl chloride fluoromethyl- piperidine benzaldehyde Compound 488 Methyl 2-amino-5- 3-(Chloromethyl)- 3-Methoxy- 4-Piperidino- iodobenzoate benzoyl chloride benzaldehyde piperidine Compound 489 Methyl 2-amino-5- 3-(Chloromethyl)- 4-Methoxy- 4-Piperidino- iodobenzoate benzoyl chloride benzaldehyde piperidine Compound 490 Methyl 2-amino-5- 3-(Chloromethyl)- 3-Hydroxy- 4-Piperidino- iodobenzoate benzoyl chloride benzaldehyde piperidine Compound 491 Methyl 2-amino-5- 3-(Chloromethyl)- 4-Hydroxy- 4-Piperidino- iodobenzoate benzoyl chloride benzaldehyde piperidine Compound 492 Methyl 2-amino-5- 3-(Chloromethyl)- 3,4-Dimethyl- 2-Mercapto- chlorobenzoate benzoyl chloride benzaldehyde ethanol Compound 493 Methyl 2-amino-5- 3-(Chloromethyl)- 3,4-Dimethyl- 2-Mercapto- chlorobenzoate benzoyl chloride benzaldehyde ethanol Compound 494 Methyl 2-amino-5- 4-Methylbenzoyl p-Tolualdehyde bromobenzoate chloride Compound 495 Methyl 2-amino-5- Picolinoyl chloride 3-Fluorobenzaldehyde bromobenzoate hydrochloride Compound 496 Methyl 2-amino-5- Picolinoyl chloride 4-Fluorobenzaldehyde bromobenzoate hydrochloride Compound 497 Methyl 2-amino-5- Picolinoyl chloride m-Tolualdehyde bromobenzoate hydrochloride Compound 498 Methyl 2-amino-5- Picolinoyl chloride p-Tolualdehyde bromobenzoate hydrochloride Compound 499 Methyl 2-amino-5- Picolinoyl chloride 3,4-Dimethyl- bromobenzoate hydrochloride benzaldehyde Compound 500 Methyl 2-amino-5- Picolinoyl chloride 4-Chloro-3-tri- bromobenzoate hydrochloride fluoromethyl- benzaldehyde Compound 501 Methyl 2-amino-5- 4-Ethoxybenzoyl 3-Fluorobenzaldehyde bromobenzoate chloride Compound 502 Methyl 2-amino-5- 4-Ethoxybenzoyl 4-Fluorobenzaldehyde bromobenzoate chloride Compound 503 Methyl 2-amino-5- 4-Ethoxybenzoyl p-Tolualdehyde bromobenzoate chloride Compound 504 Methyl 2-amino-5- 4-Ethoxybenzoyl 3,4-Dimethyl- bromobenzoate chloride benzaldehyde Compound 505 Methyl 2- Picolinoyl chloride 3-Fluorobenzaldehyde aminobenzoate hydrochloride Compound 506 Methyl 2- Picolinoyl chloride 4-Fluorobenzaldehyde aminobenzoate hydrochloride Compound 507 Methyl 2- Picolinoyl chloride 3,4-Dimethyl- aminobenzoate hydrochloride benzaldehyde Compound 508 Methyl 2- Picolinoyl chloride 4-Chloro-3-tri- aminobenzoate hydrochloride fluoromethyl- benzaldehyde Compound 509 Methyl 2-amino-5- Cyclohexane- 3-Fluorobenzaldehyde bromobenzoate carbonyl chloride Compound 510 Methyl 2-amino-5- Isoxazole-5- 3-Fluorobenzaldehyde bromobenzoate carbonyl chloride Compound 511 Methyl 2-amino-5- Isoxazole-5- m-Tolualdehyde bromobenzoate carbonyl chloride Compound 512 Methyl 2-amino-5- Isoxazole-5- 3,4-Dimethyl- bromobenzoate carbonyl chloride benzaldehyde Compound 513 Methyl 2-amino-5- Isoxazole-5- 4-Chloro-3-tri- bromobenzoate carbonyl chloride fluoromethyl- benzaldehyde Compound 514 Methyl 2- 2,5-Dimethylfuran- 3-Fluorobenzaldehyde aminobenzoate 3-carbonyl chloride Compound 515 Methyl 2- 2,5-Dimethylfuran- 4-Fluorobenzaldehyde aminobenzoate 3-carbonyl chloride Compound 516 Methyl 2- 2,5-Dimethylfuran- m-Tolualdehyde aminobenzoate 3-carbonyl chloride Compound 517 Ethyl 2-amino-4- 3,4-Dimethoxy- 3-Fluoro- methylthiophene-3- benzoyl chloride benzaldehyde carboxylate Compound 518 Ethyl 2-amino-4- 3,4-Dimethoxy- m-Tolualdehyde methylthiophene-3- benzoyl chloride carboxylate Compound 519 Ethyl 2-amino-4- 3,4-Dimethoxy- p-Tolualdehyde methylthiophene-3- benzoyl chloride carboxylate Vacant number Compound 521 Ethyl 2-amino-4- 3,4-Dimethoxy- 3,4-Dimethyl- methylthiophene-3- benzoyl chloride benzaldehyde carboxylate Compound 522 Ethyl 2-amino-4- 3,4-Dimethoxy- 4-Chloro-3-tri- methylthiophene-3- benzoyl chloride fluoromethyl- carboxylate benzaldehyde Compound 523 Methyl 3-amino-4- 3-(Chloromethyl)- 3,4-Dimethyl- 3-Mercapto- methylthiophene-2- benzoyl chloride benzaldehyde 1,2,4-triazole carboxylate Compound 524 Methyl 3-amino-4- 3-(Chloromethyl)- 3-Fluorobenzaldehyde 3-Mercapto- methylthiophene-2- benzoyl chloride 1,2,4-triazole carboxylate Compound 525 Methyl 3-amino-4- 3-(Chloromethyl)- 3,4-Dimethyl- 3-Mercapto-1- methylthiophene-2- benzoyl chloride benzaldehyde propanol carboxylate Compound 526 Methyl 3-amino-4- 3-(Chloromethyl)- p-Tolualdehyde 3-Mercapto-1- methylthiophene-2- benzoyl chloride propanol carboxylate Compound 527 Methyl 3-amino-4- 3-(Chloromethyl)- 3-Fluorobenzaldehyde 3-Mercapto-1- methylthiophene-2- benzoyl chloride propanol carboxylate Compound 528 Methyl 3-amino-4- 3-(Chloromethyl)- 4-Fluorobenzaldehyde N,N-Diethyl- methylthiophene-2- benzoyl chloride N′-methyl- carboxylate ethylene- diamine Compound 529 Methyl 3-amino-4- 3-(Chloromethyl)- 3-Fluorobenzaldehyde N,N-Diethyl- methylthiophene-2- benzoyl chloride N′-methyl- carboxylate ethylene- diamine Compound 530 Methyl 3-amino-4- 3-(Chloromethyl)- p-Methoxy- N,N-Diethyl- methylthiophene-2- benzoyl chloride benzaldehyde N′-methyl- carboxylate ethylenediamine Compound 531 Methyl 3-amino-4- 3-(Chloromethyl)- p-Methoxy- 4-Piperidino- methylthiophene-2- benzoyl chloride benzaldehyde piperidine carboxylate Compound 532 Methyl 3-amino-4- 3-(Chloromethyl)- 3,4-Dimethyl- 1-(2-Hydroxy- methylthiophene-2- benzoyl chloride benzaldehyde ethyl)- carboxylate piperazine Compound 533 Methyl 3-amino-4- 3-(Chloromethyl)- p-Tolualdehyde 1-(2-Hydroxy- methylthiophene-2- benzoyl chloride ethyl)- carboxylate piperazine Compound 534 Methyl 3-amino-4- 3-(Chloromethyl)- 4-Fluoro- 1-(2- methylthiophene-2- benzoyl chloride benzaldehyde Hydroxyethyl) carboxylate piperazine Compound 535 Methyl 3-amino-4- 3-(Chloromethyl)- 3-Fluoro- 1-(2- methylthiophene-2- benzoyl chloride benzaldehyde Hydroxyethyl) carboxylate piperazine Compound 536 Methyl 3-amino-4- 3-(Chloromethyl)- 3,4-Dimethyl- N-N-Diethyl- methylthiophene-2- benzoyl chloride benzaldehyde ethylene- carboxylate diamine Compound 537 Methyl 3-amino-4- 3-(Chloromethyl)- p-Tolualdehyde N,N-Diethyl- methylthiophene-2- benzoyl chloride ethylene- carboxylate diamine Compound 538 Methyl 3-amino-4- 3-(Chloromethyl)- 3-Fluorobenzaldehyde N,N-Diethyl- methylthiophene-2- benzoyl chloride ethylene- carboxylate diamine Compound 539 Methyl 3-amino-4- 3-(Chloromethyl)- 4-Chloro-3-tri- N,N-Diethyl- methylthiophene-2- benzoyl chloride fluoromethyl- ethylene- carboxylate benzaldehyde diamine Compound 540 Methyl 3-amino-4- 3-(Chloromethyl)- p-Tolualdehyde Diisopropanol- methylthiophene-2- benzoyl chloride amine carboxylate Compound 541 Methyl 3-amino-4- 3-(Chloromethyl)- 3,4-Dimethyl- 4-Hydroxy- methylthiophene-2- benzoyl chloride benzaldehyde piperidine carboxylate Compound 542 Methyl 3-amino-4- 3-(Chloromethyl)- 3-Fluorobenzaldehyde 4-Hydroxy- methylthiophene-2- benzoyl chloride piperidine carboxylate Compound 543 Methyl 3-amino-4- 3-(Chloromethyl)- p-Methoxy- 4-Hydroxy- methylthiophene-2- benzoyl chloride benzaldehyde piperidine carboxylate Compound 544 Methyl 2-amino-5- Picolinoyl chloride p-Tolualdehyde bromobenzoate hydrochloride Compound 545 Methyl 2- Isonicotinoyl p-Tolualdehyde aminobenzoate chloride hydrochloride Compound 546 Methyl 2-amino-5- 3-(Chloromethyl)- 4-Chloro-3-tri- 2-Mercapto- bromobenzoate benzoyl chloride fluoromethyl- ethanol benzaldehyde Compound 547 Methyl 2-amino-5- 3-(Chloromethyl)- p-Tolualdehyde 2-Mercapto- chlorobenzoate benzoyl chloride ethanol Compound 548 Methyl 2-amino-5- 3,4-Dimethoxy- 3,4-Dimethyl- bromobenzoate benzoyl chloride benzaldehyde Compound 549 Methyl 2-amino-5- 3-(Chloromethyl)- 3-Fluorobenzaldehyde Diethanol- chlorobenzoate benzoyl chloride amine Compound 550 Methyl 2-amino-5- 3-(Chloromethyl)- 4-Fluorobenaldehyde Diethanol- chlorobenzoate benzoyl chloride amine Compound 551 Ethyl 2-amino-4- 3-(Chloromethyl)- 3,4-Dimethyl- 3-Mercapto- methylthiophene-3- benzoyl chloride benzaldehyde 1,2,4-triazole carboxylate Compound 552 Ethyl 2-amino-4- 3-(Chloromethyl)- p-Tolualdehyde 3-Mercapto- methylthiophene-3- benzoyl chloride 1,2,4-triazole carboxylate Compound 553 Ethyl 2-amino-4- 3-(Chloromethyl)- 4-Fluorobenzaldehyde 3-Mercapto- methylthiophene-3- benzoyl chloride 1,2,4-triazole carboxylate Compound 554 Ethyl 2-amino-4- 3-(Chloromethyl)- 3-Fluorobenzaldehyde 3-Mercapto- methylthiophene-3- benzoyl chloride 1,2,4-triazole carboxylate Compound 555 Ethyl 2-amino-4- 3-(Chloromethyl)- 4-Chloro-3-tri- 3-Mercapto- methylthiophene-3- benzoyl chloride fluoromethyl- 1,2,4-triazole carboxylate benzaldehyde Compound 556 Ethyl 2-amino-4- 3-(Chloromethyl)- p-Methoxy- 3-Mercapto- methylthiophene-3- benzoyl chloride benzaldehyde 1,2,4-triazole carboxylate Compound 557 Ethyl 2-amino-4- 3-(Chloromethyl)- 3,4-Dimethyl- 3-Mercapto-1- methylthiophene-3- benzoyl chloride benzaldehyde propanol carboxylate Compound 558 Ethyl 2-amino-4- 3-(Chloromethyl)- p-Tolualdehyde 3-Mercapto-1- methylthiophene-3- benzoyl chloride propanol carboxylate Compound 559 Ethyl 2-amino-4- 3-(Chloromethyl)- 4-Fluorobenzaldehyde 3-Mercapto-1- methylthiophene-3- benzoyl chloride propanol carboxylate Compound 560 Ethyl 2-amino-4- 3-(Chloromethyl)- 3-Fluorobenzaldehyde 3-Mercapto-1- methylthiophene-3- benzoyl chloride propanol carboxylate Compound 561 Ethyl 2-amino-4- 3-(Chloromethyl)- 4-Chloro-3-tri- 3-Mercapto-1- methylthiophene-3- benzoyl chloride fluoromethyl- propanol carboxylate benzaldehyde Compound 562 Ethyl 2-amino-4- 3-(Chloromethyl)- p-Methoxy- 3-Mercapto-1- methylthiophene-3- benzoyl chloride benzaldehyde propanol carboxylate Compound 563 Ethyl 2-amino-4- 3-(Chloromethyl)- 3,4-Dimethyl- N,N-Diethyl- methylthiophene-3- benzoyl chloride benzaldehyde N′-methyl- carboxylate ethylene- diamine Compound 564 Ethyl 2-amino-4- 3-(Chloromethyl)- p-Tolualdehyde N,N-Diethyl- methylthiophene-3- benzoyl chloride N′-methyl- carboxylate ethylene- diamine Compound 565 Ethyl 2-amino-4- 3-(Chloromethyl)- 4-Fluorobenzaldehyde N,N-Diethyl- methylthiophene-3- benzoyl chloride N′-methyl- carboxylate ethylene- diamine Compound 566 Ethyl 2-amino-4- 3-(Chloromethyl)- 3-Fluorobenzaldehyde N,N-Diethyl- methylthiophene-3- benzoyl chloride N′-methyl- carboxylate ethylene- diamine Compound 567 Ethyl 2-amino-4- 3-(Chloromethyl) 4-Chloro-3-tri- N,N-Diethyl- methylthiophene-3- benzoyl chloride fluoromethyl- N′-methyl- carboxylate benzaldehyde ethylene- diamine Compound 568 Ethyl 2-amino-4- 3-(Chloromethyl)- p-Methoxy- N,N-Diethyl- methylthiophene-3- benzoyl chloride benzaldehyde N′-methyl- carboxylate ethylene- diamine Compound 569 Ethyl 2-amino-4- 3-(Chloromethyl)- 3,4-Dimethyl- 4-Piperidino- methylthiophene-3- benzoyl chloride benzaldehyde piperidine carboxylate Compound 570 Ethyl 2-amino-4- 3-(Chloromethyl)- p-Tolualdehyde 4-Piperidino- methylthiophene-3- benzoyl chloride piperidine carboxylate Compound 571 Ethyl 2-amino-4- 3-(Chloromethyl)- 4-Fluorobenzaldehyde 4-Piperidino- methylthiophene-3- benzoyl chloride piperidine carboxylate Compound 572 Ethyl 2-amino-4- 3-(Chloromethyl)- 3-Fluorobenzaldehyde 4-Piperidino- methylthiophene-3- benzoyl chloride piperidine carboxylate Compound 573 Ethyl 2-amino-4- 3-(Chloromethyl)- 4-Chloro-3-tri- 4-Piperidino- methylthiophene-3- benzoyl chloride fluoromethyl- piperidine carboxylate benzaldehyde Compound 574 Ethyl 2-amino-4- 3-(Chloromethyl)- p-Methoxy- 4-Piperidino- methylthiophene-3- benzoyl chloride benzaldehyde piperidine carboxylate Compound 575 Ethyl 2-amino-4- 3-(Chloromethyl)- 3,4-Dimethyl- 1-(2-Hydroxy- methylthiophene-3- benzoyl chloride benzaldehyde ethyl)- carboxylate piperazine Compound 576 Ethyl 2-amino-4- 3-(Chloromethyl)- p-Tolualdehyde 1-(2-Hydroxy- methylthiophene-3- benzoyl chloride ethyl)- carboxylate piperazine Compound 577 Ethyl 2-amino-4- 3-(Chloromethyl)- 4-Fluorobenzaldehyde 1-(2-Hydroxy- methylthiophene-3- benzoyl chloride ethyl)- carboxylate piperazine Compound 578 Ethyl 2-amino-4- 3-(Chloromethyl)- 3-Fluorobenzaldehyde 1-(2-Hydroxy- methylthiophene-3- benzoyl chloride ethyl)- carboxylate piperazine Compound 579 Ethyl 2-amino-4- 3-(Chloromethyl)- 4-Chloro-3-tri- 1-(2-Hydroxy- methylthiophene-3- benzoyl chloride fluoromethyl- ethyl)- carboxylate benzaldehyde piperazine Compound 580 Ethyl 2-amino-4- 3-(Chloromethyl)- p-Methoxy 1-(2-Hydroxy- methylthiophene-3- benzoyl chloride benzaldehyde ethyl)- carboxylate piperazine Compound 581 Ethyl 2-amino-4- 3-(Chloromethyl)- 3,4-Dimethyl- N,N-Diethyl- methylthiophene-3- benzoyl chloride benzaldehyde ethylene- carboxylate diamine Compound 582 Ethyl 2-amino-4- 3-(Chloromethyl)- p-Tolualdehyde N,N-Diethyl- methylthiophene-3- benzoyl chloride ethylene- carboxylate diamine Compound 583 Ethyl 2-amino-4- 3-(Chloromethyl)- 4-Fluorobenzaldehyde N,N-Diethyl- methylthiophene-3- benzoyl chloride ethylene- carboxylate diamine Compound 584 Ethyl 2-amino-4- 3-(Chloromethyl)- 3-Fluorobenzaldehyde N,N-Diethyl- methylthiophene-3- benzoyl chloride ethylene- carboxylate diamine Compound 585 Ethyl 2-amino-4- 3-(Chloromethyl)- 4-Chloro-3-tri- N,N-Diethyl- methylthiophene-3- benzoyl chloride fluoromethyl- ethylene- carboxylate benzaldehyde diamine Compound 586 Ethyl 2-amino-4- 3-(Chloromethyl)- p-Methoxy- N,N-Diethyl- methylthiophene-3- benzoyl chloride benzaldehyde ethylene- carboxylate diamine Compound 587 Ethyl 2-amino-4- 3-(Chloromethyl)- 3,4-Dimethyl- Diisopropanol- methylthiophene-3- benzoyl chloride benzaldehyde amine carboxylate Compound 588 Ethyl 2-amino-4- 3-(Chloromethyl)- p-Tolualdehyde Diisopropanol- methylthiophene-3- benzoyl chloride amine carboxylate Compound 589 Ethyl 2-amino-4- 3-(Chloromethyl)- 4-Fluorobenzaldehyde Diisopropanol- methylthiophene-3- benzoyl chloride amine carboxylate Compound 590 Ethyl 2-amino-4- 3-(Chloromethyl)- 3-Fluorobenzaldehyde Diisopropanol- methylthiophene-3- benzoyl chloride amine carboxylate Compound 591 Ethyl 2-amino-4- 3-(Chloromethyl)- 4-Chloro-3-tri- Diisopropanol- methylthiophene-3- benzoyl chloride fluoromethyl- amine carboxylate benzaldehyde Compound 592 Ethyl 2-amino-4- 3-(Chloromethyl)- p-Methoxy- Diisopropanol- methylthiophene-3- benzoyl chloride benzaldehyde amine carboxylate Compound 593 Ethyl 2-amino-4- 3-(Chloromethyl)- 3,4-Dimethyl- 4-Hydroxy- methylthiophene-3- benzoyl chloride benzaldehyde piperidine carboxylate Compound 594 Ethyl 2-amino-4- 3-(Chloromethyl)- p-Tolualdehyde 4-Hydroxy- methylthiophene-3- benzoyl chloride piperidine carboxylate Compound 595 Ethyl 2-amino-4- 3-(Chloromethyl)- 4-Fluorobenzaldehyde 4-Hydroxy- methylthiophene-3- benzoyl chloride piperidine carboxylate Compound 596 Ethyl 2-amino-4- 3-(Chloromethyl)- 3-Fluorobenzaldehyde 4-Hydroxy- methylthiophene-3- benzoyl chloride piperidine carboxylate Compound 597 Ethyl 2-amino-4- 3-(Chloromethyl)- 4-Chloro-3-tri- 4-Hydroxy- methylthiophene-3- benzoyl chloride fluoromethyl- piperidine carboxylate benzaldehyde Compound 598 Ethyl 2-amino-4- 3-(Chloromethyl)- p-Methoxy- 4-Hydroxy- methylthiophene-3- benzoyl chloride benzaldehyde piperidine carboxylate Compound 599 Ethyl 2-amino-4- 3-(Chloromethyl)- 3,4-Dimethyl- 4-Piperidine- methylthiophene-3- benzoyl chloride benzaldehyde methanol carboxylate Compound 600 Ethyl 2-amino-4- 3-(Chloromethyl)- p-Tolualdehyde 4-Piperidine- methylthiophene-3- benzoyl chloride methanol carboxylate Compound 601 Ethyl 2-amino-4- 3-(Chloromethyl)- 4-Fluorobenzaldehyde 4-Piperidine- methylthiophene-3- benzoyl chloride methanol carboxylate Compound 602 Ethyl 2-amino-4- 3-(Chloromethyl)- 3-Fluorobenzaldehyde 4-Piperidine- methylthiophene-3- benzoyl chloride methanol carboxylate Compound 603 Ethyl 2-amino-4- 3-(Chloromethyl)- 4-Chloro-3-tri- 4-Piperidine- methylthiophene-3- benzoyl chloride fluoromethyl- methanol carboxylate benzaldehyde Compound 604 Ethyl 2-amino-4- 3-(Chloromethyl)- p-Methoxy- 4-Piperidine- methylthiophene-3- benzoyl chloride benzaldehyde methanol carboxylate Compound 605 2-Amino-4,5,6,7-tetra- 3-(Chloromethyl)- 3,4-Dimethyl- 3-Mercapto-1- hydrobenzothiophene- benzoyl chloride benzaldehyde propanol 3-carboxylic acid ethyl ester Compound 606 2-Amino-4,5,6,7-tetra- 3-(Chloromethyl)- 4-Fluorobenzaldehyde 3-Mercapto-1- hydrobenzothiophene- benzoyl chloride propanol 3-carboxylic acid ethyl ester Compound 607 2-Amino-4,5,6,7-tetra- 3-(Chloromethyl)- 3-Fluorobenzaldehyde 3-Mercapto-1- hydrobenzothiophene- benzoyl chloride propanol 3-carboxylic acid ethyl ester Compound 608 2-Amino-4,5,6,7-tetra- 3-(Chloromethyl)- 4-Chloro-3-tri- 3-Mercapto-1- hydrobenzothiophene- benzoyl chloride fluoromethyl- propanol 3-carboxylic acid ethyl benzaldehyde ester Compound 609 2-Amino-4,5,6,7-tetra- 3-(Chloromethyl)- 3,4-Dimethyl- N,N-Diethyl- hydrobenzothiophene- benzoyl chloride benzaldehyde N′-methyl- 3-carboxylic acid ethyl ethylene- ester diamine Compound 610 2-Amino-4,5,6,7-tetra- 3-(Chloromethyl)- p-Tolualdehyde N,N-Diethyl- hydrobenzothiophene- benzoyl chloride N′-methyl- 3-carboxylic acid ethyl ethylene- ester diamine Compound 611 2-Amino-4,5,6,7-tetra- 3-(Chloromethyl)- 4-Fluorobenzaldehyde N,N-Diethyl- hydrobenzothiophene- benzoyl chloride N′-methyl- 3-carboxylic acid ethyl ethylene- ester diamine Compound 612 2-Amino-4,5,6,7-tetra- 3-(Chloromethyl)- 3-Fluorobenzaldehyde N,N-Diethyl- hydrobenzothiophene- benzoyl chloride N′-methyl- 3-carboxylic acid ethyl ethylene- ester diamine Compound 613 2-Amino-4,5,6,7-tetra- 3-(Chloromethyl)- 4-Chloro-3-tri- N,N-Diethyl- hydrobenzothiophene- benzoyl chloride fluoromethyl- N′-methyl- 3-carboxylic acid ethyl benzaldehyde ethylene- ester diamine Compound 614 2-Amino-4,5,6,7-tetra- 3-(Chloromethyl)- p-Methoxy- N,N-Diethyl- hydrobenzothiophene- benzoyl chloride benzaldehyde N′-methyl- 3-carboxylic acid ethyl ethylene- ester diamine Compound 615 2-Amino-4,5,6,7-tetra- 3-(Chloromethyl)- 3,4-Dimethyl- 4-Piperidino- hydrobenzothiophene- benzoyl chloride benzaldehyde piperidine 3-carboxylic acid ethyl ester Compound 616 2-Amino-4,5,6,7-tetra- 3-(Chloromethyl)- p-Tolualdehyde 4-Piperidino- hydrobenzothiophene- benzoyl chloride piperidine 3-carboxylic acid ethyl ester Compound 617 2-Amino-4,5,6,7-tetra- 3-(Chloromethyl)- 4-Fluorobenzaldehyde 4-Piperidino- hydrobenzothiophene- benzoyl chloride piperidine 3-carboxylic acid ethyl ester Compound 618 2-Amino-4,5,6,7-tetra- 3-(Chloromethyl)- 3-Fluorobenzaldehyde 4-Piperidino- hydrobenzothiophene- benzoyl chloride piperidine 3-carboxylic acid ethyl ester Compound 619 2-Amino-4,5,6,7-tetra- 3-(Chloromethyl)- 4-Chloro-3-tri- 4-Piperidino- hydrobenzothiophene- benzoyl chloride fluoromethyl- piperidine 3-carboxylic acid ethyl benzaldehyde ester Compound 620 2-Amino-4,5,6,7-tetra- 3-(Chloromethyl)- p-Methoxy- 4-Piperidino- hydrobenzothiophene- benzoyl chloride benzaldehyde piperidine 3-carboxylic acid ethyl ester Compound 621 2-Amino-4,5,6,7-tetra- 3-(Chloromethyl)- 3,4-Dimethyl- 4-Piperazine- hydrobenzothiophene- benzoyl chloride benzaldehyde ethanol 3-carboxylic acid ethyl ester Compound 622 2-Amino-4,5,6,7-tetra- 3-(Chloromethyl)- p-Tolualdehyde 4-Piperazine- hydrobenzothiophene- benzoyl chloride ethanol 3-carboxylic acid ethyl ester Compound 623 2-Amino-4,5,6,7-tetra- 3-(Chloromethyl)- 4-Fluorobenzaldehyde 4-Piperazine- hydrobenzothiophene- benzoyl chloride ethanol 3-carboxylic acid ethyl ester Compound 624 2-Amino-4,5,6,7-tetra- 3-(Chloromethyl)- 3-Fluorobenzaldehyde 4-Piperazine- hydrobenzothiophene- benzoyl chloride ethanol 3-carboxylic acid ethyl ester Compound 625 2-Amino-4,5,6,7-tetra- 3-(Chloromethyl)- 4-Chloro-3-tri- 4-Piperazine- hydrobenzothiophene- benzoyl chloride fluoromethyl- ethanol 3-carboxylic acid ethyl benzaldehyde ester Compound 626 2-Amino-4,5,6,7-tetra- 3-(Chloromethyl)- p-Methoxy- 4-Piperazine- hydrobenzothiophene- benzoyl chloride benzaldehyde ethanol 3-carboxylic acid ethyl ester Compound 627 2-Amino-4,5,6,7-tetra- 3-(Chloromethyl)- 3,4-Dimethyl- Diisopropanol- hydrobenzothiophene- benzoyl chloride benzaldehyde amine 3-carboxylic acid ethyl ester Compound 628 2-Amino-4,5,6,7-tetra- 3-(Chloromethyl)- p-Tolualdehyde Diisopropanol- hydrobenzothiophene- benzoyl chloride amine 3-carboxylic acid ethyl ester Compound 629 2-Amino-4,5,6,7-tetra- 3-(Chloromethyl)- 4-Fluorobenzaldehyde Diisopropanol- hydrobenzothiophene- benzoyl chloride amine 3-carboxylic acid ethyl ester Compound 630 2-Amino-4,5,6,7-tetra- 3-(Chloromethyl)- 3-Fluorobenzaldehyde Diisopropanol- hydrobenzothiophene- benzoyl chloride amine 3-carboxylic acid ethyl ester Compound 631 2-Amino-4,5,6,7-tetra- 3-(Chloromethyl)- 4-Chloro-3- Diisopropanol- hydrobenzothiophene- benzoyl chloride trifluoromethyl- amine 3-carboxylic acid ethyl benzaldehyde ester Compound 632 2-Amino-4,5,6,7-tetra- 3-(Chloromethyl)- p-Methoxy- Diisopropanol- hydrobenzothiophene- benzoyl chloride benzaldehyde amine 3-carboxylic acid ethyl ester Compound 633 2-Amino-4,5,6,7-tetra- 3-(Chloromethyl)- 3,4-Dimethyl- 4-Hydroxy- hydrobenzothiophene- benzoyl chloride benzaldehyde piperidine 3-carboxylic acid ethyl ester Compound 634 2-Amino-4,5,6,7-tetra- 3-(Chloromethyl)- p-Tolualdehyde 4-Hydroxy- hydrobenzothiophene- benzoyl chloride piperidine 3-carboxylic acid ethyl ester Compound 635 2-Amino-4,5,6,7-tetra- 3-(Chloromethyl)- 4-Fluorobenzaldehyde 4-Hydroxy- hydrobenzothiophene- benzoyl chloride piperidine 3-carboxylic acid ethyl ester Compound 636 2-Amino-4,5,6,7-tetra- 3-(Chloromethyl)- 3-Fluorobenzaldehyde 4-Hydroxy- hydrobenzothiophene- benzoyl chloride piperidine 3-carboxylic acid ethyl ester Compound 637 2-Amino-4,5,6,7-tetra- 3-(Chloromethyl)- 4-Chloro-3-tri- 4-Hydroxy- hydrobenzothiophene- benzoyl chloride fluoromethyl- piperidine 3-carboxylic acid ethyl benzaldehyde ester Compound 638 2-Amino-4,5,6,7-tetra- 3-(Chloromethyl)- p-Methoxy- 4-Hydroxy- hydrobenzothiophene- benzoyl chloride benzaldehyde piperidine 3-carboxylic acid ethyl ester Compound 639 2-Amino-4,5,6,7-tetra- 3-(Chloromethyl)- 3,4-Dimethyl- 4-Piperidine- hydrobenzothiophene- benzoyl chloride benzaldehyde methanol 3-carboxylic acid ethyl ester Compound 640 2-Amino-4,5,6,7-tetra- 3-(Chloromethyl)- p-Tolualdehyde 4-Piperidine- hydrobenzothiophene- benzoyl chloride methanol 3-carboxylic acid ethyl ester Compound 641 2-Amino-4,5,6,7-tetra- 3-(Chloromethyl)- 4-Fluorobenzaldehyde 4-Piperidine- hydrobenzothiophene- benzoyl chloride methanol 3-carboxylic acid ethyl ester Compound 642 2-Amino-4,5,6,7-tetra- 3-(Chloromethyl)- 3-Fluorobenzaldehyde 4-Piperidine- hydrobenzothiophene- benzoyl chloride methanol 3-carboxylic acid ethyl ester Compound 643 2-Amino-4,5,6,7-tetra- 3-(Chloromethyl)- 4-Chloro-3-tri- 4-Piperidine- hydrobenzothiophene- benzoyl chloride fluoromethyl- methanol 3-carboxylic acid ethyl benzaldehyde ester Compound 644 2-Amino-4,5,6,7-tetra- 3-(Chloromethyl)- p-Methoxy- 4-Piperidine- hydrobenzothiophene- benzoyl chloride benzaldehyde methanol 3-carboxylic acid ethyl ester Compound 645 Ethyl 2-amino-4- 3-(Chloromethyl)- 3,4-Dimethyl- 3-Mercapto-1- methylthiophene-3- benzoyl chloride benzaldehyde propanol carboxylate Compound 646 2-Amino-4,5,6,7-tetra- 3-(Chloromethyl)- 3,4-Dimethyl- 3-Mercapto- hydrobenzothiophene- benzoyl chloride benzaldehyde 1,2,4-triazole 3-carboxylic acid ethyl ester Compound 647 2-Amino-4,5,6,7-tetra- 3-(Chloromethyl)- p-Tolualdehyde 3-Mercapto- hydrobenzothiophene- benzoyl chloride 1,2,4-triazole 3-carboxylic acid ethyl ester Compound 648 2-Amino-4,5,6,7-tetra- 3-(Chloromethyl)- 4-Fluorobenzaldehyde 3-Mercapto- hydrobenzothiophene- benzoyl chloride 1,2,4-triazole 3-carboxylic acid ethyl ester Compound 649 2-Amino-4,5,6,7-tetra- 3-(Chloromethyl)- 3-Fluorobenzaldehyde 3-Mercapto- hydrobenzothiophene- benzoyl chloride 1,2,4-triazole 3-carboxylic acid ethyl ester Compound 650 2-Amino-4,5,6,7-tetra- 3-(Chloromethyl)- 4-Chloro-3-tri- 3-Mercapto- hydrobenzothiophene- benzoyl chloride fluoromethyl- 1,2,4-triazole 3-carboxylic acid ethyl benzaldehyde ester Compound 651 2-Amino-4,5,6,7-tetra- 3-(Chloromethyl)- p-Methoxy- 3-Mercapto- hydrobenzothiophene- benzoyl chloride benzaldehyde 1,2,4-triazole 3-carboxylic acid ethyl ester Compound 652 2-Amino-4,5,6,7-tetra- 3-(Chloromethyl)- 3,4-Dimethyl- N,N-Diethyl- hydrobenzothiophene- benzoyl chloride benzaldehyde ethylene- 3-carboxylic acid ethyl diamine ester Compound 653 2-Amino-4,5,6,7-tetra- 3-(Chloromethyl)- p-Tolualdehyde N,N-Diethyl- hydrobenzothiophene- benzoyl chloride ethylene- 3-carboxylic acid ethyl diamine ester Compound 654 2-Amino-4,5,6,7-tetra- 3-(Chloromethyl)- 4-Fluorobenzaldehyde N,N-Diethyl- hydrobenzothiophene- benzoyl chloride ethylene- 3-carboxylic acid ethyl diamine ester Compound 655 2-Amino-4,5,6,7-tetra- 3-(Chloromethyl)- 3-Fluorobenzaldehyde N,N-Diethyl- hydrobenzothiophene- benzoyl chloride ethylene- 3-carboxylic acid ethyl diamine ester Compound 656 2-Amino-4,5,6,7-tetra- 3-(Chloromethyl)- 4-Chloro-3-tri- N,N-Diethyl- hydrobenzothiophene- benzoyl chloride fluoromethyl- ethylene- 3-carboxylic acid ethyl benzaldehyde diamine ester Compound 657 2-Amino-4,5,6,7-tetra- 3-(Chloromethyl)- p-Methoxy- N,N-Diethyl- hydrobenzothiophene- benzoyl chloride benzaldehyde ethylene- 3-carboxylic acid ethyl diamine ester Compound 658 Ethyl 2- 3-(Chloromethyl)- 3,4-Dimethyl- 3-Mercapto-1- aminothiophene-3- benzoyl chloride benzaldehyde propanol carboxylate Compound 659 Ethyl 2- 3-(Chloromethyl)- p-Tolualdehyde 3-Mercapto-1- aminothiophene-3- benzoyl chloride propanol carboxylate Compound 660 Ethyl 2- 3-(Chloromethyl)- 4-Fluorobenzaldehyde 3-Mercapto-1- aminothiophene-3- benzoyl chloride propanol carboxylate Compound 661 Ethyl 2- 3-(Chloromethyl)- 3-Fluorobenzaldehyde 3-Mercapto-1- aminothiophene-3- benzoyl chloride propanol carboxylate Compound 662 Ethyl 2- 3-(Chloromethyl)- 4-Chloro-3-tri- 3-Mercapto-1- aminothiophene-3- benzoyl chloride fluoromethyl- propanol carboxylate benzaldehyde Compound 663 Ethyl 2- 3-(Chloromethyl)- p-Methoxy- 3-Mercapto-1- aminothiophene-3- benzoyl chloride benzaldehyde propanol carboxylate Compound 664 Ethyl 2- 3-(Chloromethyl)- 3,4-Dimethyl- N,N-Diethyl- aminothiophene-3- benzoyl chloride benzaldehyde N′-methyl- carboxylate ethylene- diamine Compound 665 Ethyl 2- 3-(Chloromethyl)- p-Tolualdehyde N,N-Diethyl- aminothiophene-3- benzoyl chloride N′-methyl- carboxylate ethylene- diamine Compound 666 Ethyl 2- 3-(Chloromethyl)- 4-Fluorobenzaldehyde N,N-Diethyl- aminothiophene-3- benzoyl chloride N′-methyl- carboxylate ethylene- diamine Compound 667 Ethyl 2- 3-(Chloromethyl)- 3-Fluorobenzaldehyde N,N-Diethyl- aminothiophene-3- benzoyl chloride N′-methyl- carboxylate ethylene- diamine Compound 668 Ethyl 2- 3-(Chloromethyl)- 4-Chloro-3-tri- N,N-Diethyl- aminothiophene-3- benzoyl chloride fluoromethyl- N′-methyl- carboxylate benzaldehyde ethylenediamine Compound 669 Ethyl 2- 3-(Chloromethyl)- p-Methoxy- N,N-Diethyl- aminothiophene-3- benzoyl chloride benzaldehyde N′-methyl- carboxylate ethylene- diamine Compound 670 Ethyl 2- 3-(Chloromethyl)- 3,4-Dimethyl- Diisopropanol- aminothiophene-3- benzoyl chloride benzaldehyde amine carboxylate Compound 671 Ethyl 2- 3-(Chloromethyl)- p-Tolualdehyde Diisopropanol- aminothiophene-3- benzoyl chloride amine carboxylate Compound 672 Ethyl 2- 3-(Chloromethyl)- 4-Fluorobenzaldehyde Diisopropanol- aminothiophene-3- benzoyl chloride amine carboxylate Compound 673 Ethyl 2- 3-(Chloromethyl)- 3-Fluorobenzaldehyde Diisopropanol- aminothiophene-3- benzoyl chloride amine carboxylate Compound 674 2-Amino-4,5,6,7-tetra- 3-(Chloromethyl)- 4-Chloro-3-tri- N,N-Diethyl- hydrobenzothiophene- benzoyl chloride fluoromethyl- N′-methyl- 3-carboxylic acid ethyl benzaldehyde ethylene- ester diamine Compound 675 2-Amino-4,5,6,7-tetra- 3-(Chloromethyl)- p-Methoxy- N,N-Diethyl- hydrobenzothiophene- benzoyl chloride benzaldehyde N′-methyl- 3-carboxylic acid ethyl ethylene- ester diamine Compound 676 Methyl 2-amino-5- 3-(Chloromethyl)- p-Tolualdehyde 2-Mercapto- bromobenzoate benzoyl chloride ethanol Compound 677 Methyl 2-amino-5- 3-(Chloromethyl)- p-Tolualdehyde 2-Mercapto- bromobenzoate benzoyl chloride ethanol Compound 678 Methyl 2-amino-5- 3-(Chloromethyl)- 4-Chloro-3- 2-Mercapto- bromobenzoate benzoyl chloride trifluoromethyl- ethanol benzaldehyde Compound 679 Methyl 2-amino-5- 3-(Chloromethyl)- 4-Chloro-3- 2-Mercapto- bromobenzoate benzoyl chloride trifluoromethyl- ethanol benzaldehyde Compound 680 Methyl 2-amino-5- 3-(Chloromethyl)- 3-Fluorobenzaldehyde Furfuryl chlorobenzoate benzoyl chloride mercaptan Compound 681 Methyl 2-amino-5- 3-(Chloromethyl)- 4-Fluorobenzaldehyde Furfuryl chlorobenzoate benzoyl chloride mercaptan Compound 682 Methyl 2-amino-5- 3-(Chloromethyl)- p-Tolualdehyde Furfuryl chlorobenzoate benzoyl chloride mercaptan Compound 683 Methyl 2-amino-5- 3-(Chloromethyl)- 3,4-Dimethyl- Furfuryl chlorobenzoate benzoyl chloride benzaldehyde mercaptan Compound 684 Methyl 2-amino-5- 3-(Chloromethyl)- 3,4-Dimethyl- N,N′- chlorobenzoate benzoyl chloride benzaldehyde Dimethyl-1,3- propane- diamine Compound 685 Methyl 2-amino-5- 3-(Chloromethyl)- 3-Fluorobenzaldehyde- N,N′- chlorobenzoate benzoyl chloride Dimethyl-1,3- propane- diamine Compound 686 Methyl 2-amino-5- 3-(Chloromethyl)- 3,4-Dimethyl- Furfuryl chlorobenzoate benzoyl chloride benzaldehyde mercaptan Compound 687 Methyl 2-amino-5- 3-(Chloromethyl)- 3,4-Dimethyl- Furfuryl chlorobenzoate benzoyl chloride benzaldehyde mercaptan Compound 688 Methyl 2-amino-5- 3-(Chloromethyl)- 4-Chloro-3-tri- Furfuryl chlorobenzoate benzoyl chloride fluoromethyl- mercaptan benzaldehyde Compound 689 Methyl 2-amino-5- 3-(Chloromethyl)- 4-Chloro-3-tri- Furfuryl chlorobenzoate benzoyl chloride fluoromethyl- mercaptan benzaldehyde Compound 690 Methyl 2-amino-5- 3-(Chloromethyl)- 4-Chloro-3-tri- N,N′- chlorobenzoate benzoyl chloride fluoromethyl- Dimethyl-1,6- benzaldehyde hexane- diamine Compound 691 Methyl 2-amino-5- 3-(Chloromethyl)- 3-Fluorobenzaldehyde 2-Mercapto- chlorobenzoate benzoyl chloride ethane- sulfonic acid sodium salt Compound 692 Methyl 2-amino-5- 3-(Chloromethyl)- m-Tolualdehyde 2-Mercapto- chlorobenzoate benzoyl chloride ethane- sulfonic acid sodium salt Compound 693 Methyl 2-amino-5- 3-(Chloromethyl)- p-Tolualdehyde 2-Mercapto- chlorobenzoate benzoyl chloride ethane- sulfonic acid sodium salt Compound 694 Methyl 2-amino-5- 3-(Chloromethyl)- 3,4-Dimethyl- 2-Mercapto- chlorobenzoate benzoyl chloride benzaldehyde ethane- sulfonic acid sodium salt Compound 695 Methyl 2-amino-5- 3-(Chloromethyl)- 4-Fluorobenzaldehyde 2-Mercapto- bromobenzoate benzoyl chloride ethanol Compound 696 Methyl 2-amino-5- 3-(Chloromethyl)- p-Tolualdehyde 2-Mercapto- bromobenzoate benzoyl chloride ethanol Compound 697 Methyl 2-amino-5- 3-(Chloromethyl)- 3,4-Dimethyl- 2-Mercapto- bromobenzoate benzoyl chloride benzaldehyde ethanol Compound 698 Methyl 2-amino-5- 3-(Chloromethyl)- 4-Chloro-3-tri- 2-Mercapto- bromobenzoate benzoyl chloride fluoromethyl- ethanol benzaldehyde Compound 699 Methyl 2-amino-5- 3-(Chloromethyl)- m-Tolualdehyde Furfuryl chlorobenzoate benzoyl chloride mercaptan Compound 700 Methyl 2-amino-5- 3-(Chloromethyl)- 4-Chloro-3- Furfuryl chlorobenzoate benzoyl chloride trifluoromethyl- mercaptan benzaldehyde Compound 701 Methyl 2-amino-5- 3-(Chloromethyl)- 4-Fluorobenzaldehyde N,N′- chlorobenzoate benzoyl chloride Dimethyl-1,3- propane- diamine Compound 702 Methyl 2-amino-5- 3-(Chloromethyl)- p-Tolualdehyde N,N′- chlorobenzoate benzoyl chloride Dimethyl-1,3- propane- diamine Compound 703 Methyl 2-amino-5- 3-(Chloromethyl)- 4-Chloro-3- 2-Mercapto- chlorobenzoate benzoyl chloride trifluoromethyl- ethane- benzaldehyde sulfonic acid sodium salt Compound 704 Methyl 2-amino-5- 3-(Chloromethyl)- 3-Fluorobenzaldehyde N,N′- chlorobenzoate benzoyl chloride Dimethyl-1,6- hexane- diamine Compound 705 Methyl 2-amino-5- 3-(Chloromethyl)- m-Tolualdehyde N,N′- chlorobenzoate benzoyl chloride Dimethyl-1,6- hexane- diamine Compound 706 Methyl 2-amino-5- 3-(Chloromethyl)- p-Tolualdehyde N,N′- chlorobenzoate benzoyl chloride Dimethyl-1,6- hexane- diamine Compound 707 Methyl 3-amino-4- 3-(Chloromethyl)- 4-Chloro-3- Diisopropanol- methylthiophene-2- benzoyl chloride trifluoromethyl- amine carboxylate benzaldehyde Compound 708 Methyl 2-amino-5- 3-(Chloromethyl)- 4-Fluorobenzaldehyde 2-Mercapto- chlorobenzoate benzoyl chloride ethane- sulfonic acid sodium salt Compound 709 Methyl 2-amino-5- 3-(Chloromethyl)- 4-Chloro-3- 2-Mercapto- chlorobenzoate benzoyl chloride trifluoromethyl- ethane- benzaldehyde sulfonic acid sodium salt Compound 710 Methyl 3-amino-4- 3-(Chloromethyl)- p-Tolualdehyde N,N-Diethyl- methylthiophene-2- benzoyl chloride N′-methyl- carboxylate ethylene- diamine Compound 711 Methyl 3-amino-4- 3-(Chloromethyl)- 3,4-Dimethyl- N,N-Diethyl- methylthiophene-2- benzoyl chloride benzaldehyde N′-methyl- carboxylate ethylene- diamine Compound 712 Methyl 3-amino-4- 3-(Chloromethyl)- p-Methoxy- N,N-Diethyl- methylthiophene-2- benzoyl chloride benzaldehyde N′-methyl- carboxylate ethylene- diamine Compound 713 Methyl 2-amino-5- 4-(Chloromethyl)- 3-Fluorobenzaldehyde 4-(2-Amino- bromobenzoate benzoyl chloride ethyl)- morpholine Compound 714 Methyl 2-amino-5- 4-(Chloromethyl)- 4-Chloro-3- 4-(2-Amino- bromobenzoate benzoyl chloride trifluoromethyl- ethyl)- benzaldehyde morpholine Compound 715 Methyl 2-amino-5- 4-(Chloromethyl)- p-Methoxy- 4-(2-Amino- bromobenzoate benzoyl chloride benzaldehyde ethyl)- morpholine Compound 716 Methyl 2-amino-5- 4-(Chloromethyl)- m-Methoxy- 4-(2-Amino- bromobenzoate benzoyl chloride benzaldehyde ethyl)- morpholine Compound 717 Methyl 2-amino-5- 4-(Chloromethyl)- 3,4-Dimethyl- 1-(4-Fluoro- bromobenzoate benzoyl chloride benzaldehyde phenyl)- piperazine Compound 718 Methyl 2-amino-5- 4-(Chloromethyl)- m-Tolualdehyde Diisopropanol- bromobenzoate benzoyl chloride amine Compound 719 Methyl 2-amino-5- 4-(Chloromethyl)- 4-Fluorobenzaldehyde Diisopropanol- bromobenzoate benzoyl chloride amine Compound 720 Methyl 2-amino-5- 4-(Chloromethyl)- 3-Fluorobenzaldehyde Diisopropanol- bromobenzoate benzoyl chloride amine Compound 721 Methyl 2-amino-5- 4-(Chloromethyl)- 4-Chloro-3- Diisopropanol- bromobenzoate benzoyl chloride trifluoromethyl- amine benzaldehyde Compound 722 Methyl 2-amino-5- 4-(Chloromethyl)- p-Methoxy- Diisopropanol- bromobenzoate benzoyl chloride benzaldehyde amine Compound 723 Methyl 2-amino-5- 4-(Chloromethyl)- m-Methoxy- Diisopropanol- bromobenzoate benzoyl chloride benzaldehyde amine Compound 724 Methyl 2-amino-5- 4-(Chloromethyl)- 3,4-Dimethyl- Cineferin bromobenzoate benzoyl chloride benzaldehyde Compound 725 Methyl 2-amino-5- 4-(Chloromethyl)- 3-Fluorobenzaldehyde Cineferin bromobenzoate benzoyl chloride Compound 726 Methyl 2-amino-5- 4-(Chloromethyl)- 4-Chloro-3- Cineferin bromobenzoate benzoyl chloride trifluoromethyl- benzaldehyde Compound 727 Methyl 2-amino-5- 4-(Chloromethyl)- m-Methoxy- Cineferin bromobenzoate benzoyl chloride benzaldehyde Compound 728 Methyl 2-amino-5- 4-(Chloromethyl)- p-Tolualdehyde N-(2-(1- bromobenzoate benzoyl chloride Piperazino)- acetyl)- morpholine Compound 729 Methyl 2-amino-5- 4-(Chloromethyl)- m-Tolualdehyde N-(2-(1- bromobenzoate benzoyl chloride Piperazino)- acetyl)- morpholine Compound 730 Methyl 2-amino-5- 4-(Chloromethyl)- 4-Fluorobenzaldehyde N-(2-(1- bromobenzoate benzoyl chloride Piperazino)- acetyl)- morpholine Compound 731 Methyl 2-amino-5- 4-(Chloromethyl)- 3-Fluorobenzaldehyde N-(2-(1- bromobenzoate benzoyl chloride Piperazino)- acetyl)- morpholine Compound 732 Methyl 2-amino-5- 4-(Chloromethyl)- m-Methoxy- N-(2-(1- bromobenzoate benzoyl chloride benzaldehyde Piperazino)- acetyl)- morpholine Compound 733 Methyl 2-amino-5- 4-(Chloromethyl)- 3,4-Dimethyl- Bis(2-ethoxy- bromobenzoate benzoyl chloride benzaldehyde ethyl)-amine Compound 734 Methyl 2-amino-5- 4-(Chloromethyl)- p-Tolualdehyde Bis(2-ethoxy- bromobenzoate benzoyl chloride ethyl)-amine Compound 735 Methyl 2-amino-5- 4-(Chloromethyl)- m-Tolualdehyde Bis(2-ethoxy- bromobenzoate benzoyl chloride ethyl)-amine Compound 736 Methyl 2-amino-5- 4-(Chloromethyl)- 4-Fluorobenzaldehyde Bis(2-ethoxy- bromobenzoate benzoyl chloride ethyl)amine Compound 737 Methyl 2-amino-5- 4-(Chloromethyl)- 3-Fluorobenzaldehyde Bis(2-ethoxy- bromobenzoate benzoyl chloride ethyl)amine Compound 738 Methyl 2-amino-5- 4-(Chloromethyl)- 4-Chloro-3- Bis(2-ethoxy- bromobenzoate benzoyl chloride trifluoromethyl- ethyl)amine benzaldehyde Compound 739 Methyl 2-amino-5- 4-(Chloromethyl)- p-Methoxybenzaldehyde Bis(2-ethoxy- bromobenzoate benzoyl chloride ethyl)amine Compound 740 Methyl 2-amino-5- 4-(Chloromethyl)- m-Methoxy- Bis(2-ethoxy- bromobenzoate benzoyl chloride benzaldehyde ethyl)amine Compound 741 Methyl 2-amino-5- 4-(Chloromethyl)- p-Tolualdehyde 4-Piperidine- bromobenzoate benzoyl chloride ethanol Compound 742 Methyl 2-amino-5- 4-(Chloromethyl)- m-Tolualdehyde- 4-Piperidine- bromobenzoate benzoyl chloride ethanol Compound 743 Methyl 2-amino-5- 4-(Chloromethyl)- 4-Fluorobenzaldehyde 4-Piperidine- bromobenzoate benzoyl chloride ethanol Compound 744 Methyl 2-amino-5- 4-(Chloromethyl)- 3-Fluorobenzaldehyde 4-Piperidine- bromobenzoate benzoyl chloride ethanol Compound 745 Methyl 2-amino-5- 4-(Chloromethyl)- 4-Chloro-3- 4-Piperidine- bromobenzoate benzoyl chloride trifluoromethyl- ethanol benzaldehyde Compound 746 Methyl 2-amino-5- 4-(Chloromethyl)- m-Methoxybenzaldehyde- 4-Piperidine- bromobenzoate benzoyl chloride ethanol Compound 747 Methyl 2-amino-5- 4-(Chloromethyl)- 4-Chloro-3- 2-Morpholine- bromobenzoate benzoyl chloride trifluoromethyl- 4-yl-1-phenyl- benzaldehyde ethylamine Compound 748 Methyl 2-amino-5- 4-(Chloromethyl)- p-Methoxy- 2-Morpholine- bromobenzoate benzoyl chloride benzaldehyde 4-yl-1-phenyl- ethylamine Compound 749 Methyl 2-amino-5- 4-(Chloromethyl)- 3,4-Dimethyl- 4-Amino-1,2- bromobenzoate benzoyl chloride benzaldehyde diethyl- pyrazolidine Compound 750 Methyl 2-amino-5- 4-(Chloromethyl)- 3,4-Dimethyl- 4-Amino-1,2- bromobenzoate benzoyl chloride benzaldehyde diethyl- pyrazolidine Compound 751 Methyl 2-amino-5- 4-(Chloromethyl)- 3-Fluorobenzaldehyde- 4-Amino-1,2- bromobenzoate benzoyl chloride diethyl- pyrazolidine Compound 752 Methyl 2-amino-5- 4-(Chloromethyl)- 3-Fluorobenzaldehyde- 4-Amino-1,2- bromobenzoate benzoyl chloride diethyl- pyrazolidine Compound 753 Methyl 2-amino-5- 4-(Chloromethyl)- 4-Chloro-3- 4-Amino-1,2- bromobenzoate benzoyl chloride trifluoromethyl- diethyl- benzaldehyde pyrazolidine Compound 754 Methyl 2-amino-5- 4-(Chloromethyl)- 4-Chloro-3- 4-Amino-1,2- bromobenzoate benzoyl chloride trifluoromethyl- diethyl- benzaldehyde pyrazolidine Compound 755 Methyl 2-amino-5- 4-(Chloromethyl)- p-Methoxy- 4-Amino-1,2- bromobenzoate benzoyl chloride benzaldehyde diethyl- pyrazolidine Compound 756 Methyl 2-amino-5- 4-(Chloromethyl)- p-Methoxy- 4-Amino-1,2- bromobenzoate benzoyl chloride benzaldehyde diethyl- pyrazolidine Compound 757 Methyl 2-amino-5- 4-(Chloromethyl)- 3,4-Dimethyl- N-(3-Amino- bromobenzoate benzoyl chloride benzaldehyde propyl)-N- methylaniline Compound 758 Methyl 2-amino-5- 4-(Chloromethyl)- p-Tolualdehyde N-(3-Amino- bromobenzoate benzoyl chloride propyl)-N- methylaniline Compound 759 Methyl 2-amino-5- 4-(Chloromethyl)- 4-Fluorobenzaldehyde N-(3-Amino- bromobenzoate benzoyl chloride propyl)-N- methylaniline Compound 760 Methyl 2-amino-5- 4-(Chloromethyl)- 3-Fluorobenzaldehyde N-(3-Amino- bromobenzoate benzoyl chloride propyl)-N- methylaniline Compound 761 Methyl 2-amino-5- 4-(Chloromethyl)- 4-Chloro-3- N-(3-Amino- bromobenzoate benzoyl chloride trifluoromethyl- propyl)-N- benzaldehyde methylaniline Compound 762 Methyl 2-amino-5- 4-(Chloromethyl)- p-Methoxy N-(3-Amino- bromobenzoate benzoyl chloride benzaldehyde propyl)-N- methylaniline Compound 763 Methyl 2-amino-5- 4-(Chloromethyl)- m-Methoxy N-(3-Amino- bromobenzoate benzoyl chloride benzaldehyde propyl)-N- methylaniline Compound 764 Methyl 2-amino-5- 4-(Chloromethyl)- 3,4-Dimethyl- 2-(Ethylthio)- bromobenzoate benzoyl chloride benzaldehyde ethylamine Compound 765 Methyl 2-amino-5- 4-(Chloromethyl)- p-Tolualdehyde 2-(Ethylthio)- bromobenzoate benzoyl chloride ethylamine Compound 766 Methyl 2-amino-5- 4-(Chloromethyl)- m-Tolualdehyde 2-(Ethylthio)- bromobenzoate benzoyl chloride ethylamine Compound 767 Methyl 2-amino-5- 4-(Chloromethyl)- 4-Fluorobenzaldehyde 2-(Ethylthio)- bromobenzoate benzoyl chloride ethylamine Compound 768 Methyl 2-amino-5- 4-(Chloromethyl)- 4-Fluorobenzaldehyde 2-(Ethylthio)- bromobenzoate benzoyl chloride ethylamine Compound 769 Methyl 2-amino-5- 4-(Chloromethyl)- 4-Chloro-3- 2-(Ethylthio)- bromobenzoate benzoyl chloride trifluoromethyl- ethylamine benzaldehyde Compound 770 Methyl 2-amino-5- 4-(Chloromethyl)- p-Methoxy- 2-(Ethylthio)- bromobenzoate benzoyl chloride benzaldehyde ethylamine Compound 771 Methyl 2-amino-5- 4-(Chloromethyl)- m-Methoxy- 2-(Ethylthio)- bromobenzoate benzoyl chloride benzaldehyde ethylamine Compound 772 Methyl 2-amino-5- 4-(Chloromethyl)- 3,4-Dimethyl- 1-(2-Pyridyl)- bromobenzoate benzoyl chloride benzaldehyde piperazine Compound 773 Methyl 2-amino-5- 4-(Chloromethyl)- p-Tolualdehyde 1-(2-Pyridyl)- bromobenzoate benzoyl chloride piperazine Compound 774 Methyl 2-amino-5- 4-(Chloromethyl)- 4-Fluorobenzaldehyde 1-(2-Pyridyl)- bromobenzoate benzoyl chloride piperazine Compound 775 Methyl 2-amino-5- 4-(Chloromethyl)- 3-Fluorobenzaldehyde 1-(2-Pyridyl)- bromobenzoate benzoyl chloride piperazine Compound 776 Methyl 2-amino-5- 4-(Chloromethyl)- 4-Chloro-3- 1-(2-Pyridyl)- bromobenzoate benzoyl chloride trifluoromethyl- piperazine benzaldehyde Compound 777 Methyl 2-amino-5- 4-(Chloromethyl)- p-Methoxy- 1-(2-Pyridyl)- bromobenzoate benzoyl chloride benzaldehyde piperazine Compound 778 Methyl 2-amino-5- 4-(Chloromethyl)- m-Methoxy- 1-(2-Pyridyl)- bromobenzoate benzoyl chloride benzaldehyde piperazine Compound 779 Ethyl 2- 3-(Chloromethyl)- 4-Chloro-3-tri- Diisopropanol- aminothiophene-3- benzoyl chloride fluoromethyl- amine carboxylate benzaldehyde Compound 780 Ethyl 2- 3-(Chloromethyl)- p-Methoxy- Diisopropanol- aminothiophene-3- benzoyl chloride benzaldehyde amine carboxylate Compound 781 Methyl 2-amino-4- 3-(Chloromethyl)- 3,4-Dimethyl- 2-Mercapto- methylthiophene-3- benzoyl chloride benzaldehyde ethane- carboxylate sulfonic acid Compound 782 Methyl 2-amino-4- 3-(Chloromethyl)- p-Tolualdehyde 2-Mercapto- methylthiophene-3- benzoyl chloride ethane- carboxylate sulfonic acid Compound 783 Methyl 2-amino-4- 3-(Chloromethyl)- 4-Fluorobenzaldehyde 2-Mercapto- methylthiophene-3- benzoyl chloride ethane- carboxylate sulfonic acid Compound 784 Methyl 2-amino-4- 3-(Chloromethyl)- 4-Chloro-3- 2-Mercapto- methylthiophene-3- benzoyl chloride trifluoromethyl- ethane- carboxylate benzaldehyde sulfonic acid Compound 785 Methyl 2-amino-4- 3-(Chloromethyl)- p-Methoxy- 2-Mercapto- methylthiophene-3- benzoyl chloride benzaldehyde ethane- carboxylate sulfonic acid Compound 786 Methyl 2-amino-4- 3-(Chloromethyl)- 3,4-Dimethyl- Diethanol- methylthiophene-3- benzoyl chloride benzaldehyde amine carboxylate Compound 787 Methyl 2-amino-4- 3-(Chloromethyl)- p-Tolualdehyde Diethanol- methylthiophene-3- benzoyl chloride amine carboxylate Compound 788 Methyl 2-amino-4- 3-(Chloromethyl)- 4-Fluorobenzaldehyde Diethanol- methylthiophene-3- benzoyl chloride amine carboxylate Compound 789 Methyl 2-amino-4- 3-(Chloromethyl)- 3-Fluorobenzaldehyde Diethanol- methylthiophene-3- benzoyl chloride amine carboxylate Compound 790 Methyl 2-amino-4- 3-(Chloromethyl)- 4-Chloro-3-tri- Diethanol- methylthiophene-3- benzoyl chloride fluoromethyl- amine carboxylate benzaldehyde Compound 791 Methyl 2-amino-4- 3-(Chloromethyl)- p-Methoxy- Diethanol- methylthiophene-3- benzoyl chloride benzaldehyde amine carboxylate Compound 792 Ethyl-2-amino- 3-(Chloromethyl)- 3,4-Dimethyl- Diisopropanol- benzo(B)thiophene- benzoyl chloride benzaldehyde amine 3-carboxylate Compound 793 Ethyl-2-amino- 3-(Chloromethyl)- p-Tolualdehyde Diisopropanol- benzo(B)thiophene- benzoyl chloride amine 3-carboxylate Compound 794 Ethyl-2-amino- 3-(Chloromethyl)- 4-Fluorobenzaldehyde Diisopropanol- benzo(B)thiophene- benzoyl chloride amine 3-carboxylate Compound 795 Ethyl-2-amino- 3-(Chloromethyl)- 3-Fluorobenzaldehyde Diisopropanol- benzo(B)thiophene- benzoyl chloride amine 3-carboxylate Compound 796 Ethyl-2-amino- 3-(Chloromethyl)- 4-Chloro-3- Diisopropanol- benzo(B)thiophene- benzoyl chloride trifluoromethyl- amine 3-carboxylate benzaldehyde Compound 797 Ethyl-2-amino- 3-(Chloromethyl)- p-Methoxy- Diisopropanol- benzo(B)thiophene- benzoyl chloride benzaldehyde amine 3-carboxylate Compound 798 Ethyl-2-amino- 3-(Chloromethyl)- 3,4-Dimethyl- 4-Piperidine- benzo(B)thiophene- benzoyl chloride benzaldehyde methanol 3-carboxylate Compound 799 Ethyl-2-amino- 3-(Chloromethyl)- p-Tolualdehyde 4-Piperidine- benzo(B)thiophene- benzoyl chloride methanol 3-carboxylate Compound 800 Ethyl-2-amino- 3-(Chloromethyl)- 4-Fluorobenzaldehyde 4-Piperidine- benzo(B)thiophene- benzoyl chloride methanol 3-carboxylate Compound 801 Ethyl-2-amino- 3-(Chloromethyl)- 3-Fluorobenzaldehyde 4-Piperidine- benzo(B)thiophene- benzoyl chloride methanol 3-carboxylate Compound 802 Ethyl-2-amino- 3-(Chloromethyl)- 4-Chloro-3- 4-Piperidine- benzo(B)thiophene- benzoyl chloride trifluoromethyl- methanol 3-carboxylate benzaldehyde Compound 803 Ethyl-2-amino- 3-(Chloromethyl)- p-Methoxy- 4-Piperidine- benzo(B)thiophene- benzoyl chloride benzaldehyde methanol 3-carboxylate Compound 804 Ethyl-2- 3-(Chloromethyl)- 3,4-Dimethyl- Diisopropanol- aminocyclopenta(B)- benzoyl chloride benzaldehyde amine thiophene-3- carboxylate Compound 805 Ethyl-2- 3-(Chloromethyl)- p-Tolualdehyde Diisopropanol- aminocyclopenta(B)- benzoyl chloride amine thiophene-3- carboxylate Compound 806 Ethyl-2- 3-(Chloromethyl)- 3-Fluorobenzaldehyde Diisopropanol- aminocyclopenta(B)- benzoyl chloride amine thiophene-3- carboxylate Compound 807 Ethyl-2- 3-(Chloromethyl)- 4-Fluorobenzaldehyde Diisopropanol- aminocyclopenta(B)- benzoyl chloride amine thiophene-3- carboxylate Compound 808 Ethyl-2- 3-(Chloromethyl)- 4-Chloro-3- Diisopropanol- aminocyclopenta(B)- benzoyl chloride trifluoromethyl- amine thiophene-3- benzaldehyde carboxylate Compound 809 Ethyl-2- 3-(Chloromethyl)- p-Methoxy- Diisopropanol- aminocyclopenta(B)- benzoyl chloride benzaldehyde amine thiophene-3- carboxylate Compound 810 Ethyl-2- 3-(Chloromethyl)- 3,4-Dimethyl- N,N-Diethyl- aminocyclopenta(B)- benzoyl chloride benzaldehyde ethylene- thiophene-3- diamine carboxylate Compound 811 Ethyl-2- 3-(Chloromethyl)- p-Tolualdehyde N,N-Diethyl- aminocyclopenta(B)- benzoyl chloride ethylene- thiophene-3- diamine carboxylate Compound 812 Ethyl-2- 3-(Chloromethyl)- 3-Fluorobenzaldehyde N,N-Diethyl- aminocyclopenta(B)- benzoyl chloride ethylene- thiophene-3- diamine carboxylate Compound 813 Ethyl-2- 3-(Chloromethyl)- 4-Fluorobenzaldehyde N,N-Diethyl- aminocyclopenta(B)- benzoyl chloride ethylene- thiophene-3- diamine carboxylate Compound 814 Ethyl-2- 3-(Chloromethyl)- 4-Chloro-3- N,N-Diethyl- aminocyclopenta(B)- benzoyl chloride trifluoromethyl- ethylene- thiophene-3- benzaldehyde diamine carboxylate Compound 815 Ethyl-2- 3-(Chloromethyl)- p-Methoxy- N,N-Diethyl- aminocyclopenta(B)- benzoyl chloride benzaldehyde ethylene- thiophene-3- diamine carboxylate Compound 816 Ethyl-2- 3-(Chloromethyl)- 3,4-Dimethyl- 4-Piperidine- aminocyclopenta(B)- benzoyl chloride benzaldehyde methanol thiophene-3- carboxylate Compound 817 Ethyl-2- 3-(Chloromethyl)- p-Tolualdehyde 4-Piperidine- aminocyclopenta(B)- benzoyl chloride methanol thiophene-3- carboxylate Compound 818 Ethyl-2- 3-(Chloromethyl)- 4-Fluorobenzaldehyde 4-Piperidine- aminocyclopenta(B)- benzoyl chloride methanol thiophene-3- carboxylate Compound 819 Ethyl-2- 3-(Chloromethyl)- 3-Fluorobenzaldehyde 4-Piperidine- aminocyclopenta(B)- benzoyl chloride methanol thiophene-3- carboxylate Compound 820 Ethyl-2- 3-(Chloromethyl)- 4-Chloro-3- 4-Piperidine- aminocyclopenta(B)- benzoyl chloride trifluoromethyl- methanol thiophene-3- benzaldehyde carboxylate Compound 821 Ethyl-2- 3-(Chloromethyl)- p-Methoxy- 4-Piperidine- aminocyclopenta(B)- benzoyl chloride benzaldehyde methanol thiophene-3- carboxylate Compound 822 Methyl 2-amino-4- 3-(Chloromethyl)- 3,4-Dimethyl- Dimethyl- methylthiophene-3- benzoyl chloride benzaldehyde amine carboxylate hydrochloride Compound 823 Methyl 2-amino-4- 3-(Chloromethyl)- p-Tolualdehyde Dimethyl- methylthiophene-3- benzoyl chloride amine carboxylate hydrochloride Compound 824 Methyl 2-amino-4- 3-(Chloromethyl)- 4-Chloro-3- Dimethyl- methylthiophene-3- benzoyl chloride trifluoromethyl- amine carboxylate benzaldehyde hydrochloride Compound 825 Methyl 2-amino-4- 3-(Chloromethyl)- p-Methoxy- Dimethyl- methylthiophene-3- benzoyl chloride benzaldehyde amine carboxylate hydrochloride Compound 826 Methyl 2-amino-4- 3-(Chloromethyl)- 3,4-Dimethyl- 1-(2- methylthiophene-3- benzoyl chloride benzaldehyde Pyrimidyl)- carboxylate piperazine Compound 827 Methyl 2-amino-4- 3-(Chloromethyl)- p-Tolualdehyde 1-(2- methylthiophene-3- benzoyl chloride Pyrimidyl)- carboxylate piperazine Compound 828 Methyl 2-amino-4- 3-(Chloromethyl)- 4-Fluorobenzaldehyde 1-(2- methylthiophene-3- benzoyl chloride Pyrimidyl)- carboxylate piperazine Compound 829 Methyl 2-amino-4- 3-(Chloromethyl)- 3-Fluorobenzaldehyde 1-(2- methylthiophene-3- benzoyl chloride Pyrimidyl)- carboxylate piperazine Compound 830 Methyl 2-amino-4- 3-(Chloromethyl)- 4-Chloro-3- 1-(2- methylthiophene-3- benzoyl chloride trifluoromethyl Pyrimidyl)- carboxylate benzaldehyde piperazine Compound 831 Methyl 2-amino-4- 3-(Chloromethyl)- p-Methoxy- 1-(2- methylthiophene-3- benzoyl chloride benzaldehyde Pyrimidyl)- carboxylate piperazine Compound 832 Methyl 2-amino-4- 3-(Chloromethyl)- 3,4-Dimethyl- 1,4-Dioxa-8- methylthiophene-3- benzoyl chloride benzaldehyde azaspiro[4,5]decane carboxylate Compound 833 Methyl 2-amino-4- 3-(Chloromethyl)- p-Tolualdehyde 1,4-Dioxa-8- methylthiophene-3- benzoyl chloride azaspiro[4,5]decane carboxylate Compound 834 Methyl 2-amino-4- 3-(Chloromethyl)- 4-Fluorobenzaldehyde 1,4-Dioxa-8- methylthiophene-3- benzoyl chloride azaspiro[4,5]decane carboxylate Compound 835 Methyl 2-amino-4- 3-(Chloromethyl)- 3-Fluorobenzaldehyde 1,4-Dioxa-8- methylthiophene-3- benzoyl chloride azaspiro[4,5]decane carboxylate Compound 836 Methyl 2-amino-4- 3-(Chloromethyl)- 4-Chloro-3- 1,4-Dioxa-8- methylthiophene-3- benzoyl chloride trifluoromethyl- azaspiro[4,5]decane carboxylate benzaldehyde Compound 837 Methyl 2-amino-4- 3-(Chloromethyl)- p-Methoxy- 1,4-Dioxa-8- methylthiophene-3- benzoyl chloride benzaldehyde azaspiro[4,5]decane carboxylate Compound 838 Methyl 2-amino-4- 3-(Chloromethyl)- 3,4-Dimethyl- 1,1,7,7- methylthiophene-3- benzoyl chloride benzaldehyde Tetraethyl- carboxylate diethylene- triamine Compound 839 Methyl 2-amino-4- 3-(Chloromethyl)- p-Tolualdehyde 1,1,7,7- methylthiophene-3- benzoyl chloride Tetraethyl- carboxylate diethylene- triamine Compound 840 Methyl 2-amino-4- 3-(Chloromethyl)- 4-Fluorobenzaldehyde 1,1,7,7- methylthiophene-3- benzoyl chloride Tetraethyl- carboxylate diethylene- triamine Compound 841 Methyl 2-amino-4- 3-(Chloromethyl)- 3-Fluorobenzaldehyde 1,1,7,7- methylthiophene-3- benzoyl chloride Tetraethyl- carboxylate diethylene- triamine Compound 842 Methyl 2-amino-4- 3-(Chloromethyl)- 4-Chloro-3- 1,1,7,7- methylthiophene-3- benzoyl chloride trifluoromethyl Tetraethyl- carboxylate benzaldehyde diethylene- triamine Compound 843 Methyl 2-amino-4- 3-(Chloromethyl)- p-Methoxy- 1,1,7,7- methylthiophene-3- benzoyl chloride benzaldehyde Tetraethyl- carboxylate diethylene- triamine Compound 844 Ethyl 2-amino-4,5- 3-(Chloromethyl)- 3,4-Dimethyl- Diisopropanol- dimethylthiophene- benzoyl chloride benzaldehyde amine 3-carboxylate Compound 845 Ethyl 2-amino-4,5- 3-(Chloromethyl)- p-Tolualdehyde Diisopropanol- dimethylthiophene- benzoyl chloride amine 3-carboxylate Compound 846 Ethyl 2-amino-4,5- 3-(Chloromethyl)- 4-Fluoro- Diisopropanol- dimethylthiophene- benzoyl chloride benzaldehyde amine 3-carboxylate Compound 847 Ethyl 2-amino-4,5- 3-(Chloromethyl)- 4-Chloro-3- Diisopropanol- dimethylthiophene- benzoyl chloride trifluoromethyl- amine 3-carboxylate benzaldehyde Compound 848 Ethyl 2-amino-4,5- 3-(Chloromethyl)- p-Methoxy- Diisopropanol- dimethylthiophene- benzoyl chloride benzaldehyde amine 3-carboxylate Compound 849 Ethyl 2-amino- 3-(Chloromethyl)- 4-Chloro-3- 1,1,7,7- 4,5,6,7-tetrahydro- benzoyl chloride trifluoromethyl- Tetraethyl- benzo(B)thiophene- benzaldehyde diethylene- 3-carboxylate triamine Compound 850 Ethyl 2-amino- 3-(Chloromethyl)- p-Methoxy- 1,1,7,7- 4,5,6,7-tetrahydro- benzoyl chloride benzaldehyde Tetraethyl- benzo(B)thiophene- diethylene- 3-carboxylate triamine Compound 851 Methyl 2-amino-4- 3-(Chloromethyl)- 4-Chloro-3- Diisopropanol- methylthiophene-3- benzoyl chloride trifluoromethyl- amine carboxylate benzaldehyde Compound 852 Methyl 2-amino-4- 3-(Chloromethyl)- p-Methoxy- Diisopropanol- methylthiophene-3- benzoyl chloride benzaldehyde amine carboxylate Compound 853 2-Amino-5- 3-(Chloromethyl)- 4-Chloro-3- Diisopropanol- fluorobenzoic acid benzoyl chloride trifluoromethyl- amine methyl ester benzaldehyde Compound 854 2-Amino-5- 3-(Chloromethyl)- p-Methoxy- Diisopropanol- fluorobenzoic acid benzoyl chloride benzaldehyde amine methyl ester Compound 855 Ethyl 2-amino- 3-(Chloromethyl)- 4-Chloro-3- 1,1,7,7- 4,5,6,7-tetrahydro- benzoyl chloride trifluoromethyl- Tetraethyl- benzo(B)thiophene- benzaldehyde diethylene- 3-carboxylate triamine Compound 856 Ethyl 2-amino- 3-(Chloromethyl)- p-Methoxy- 1,1,7,7- 4,5,6,7-tetrahydro- benzoyl chloride benzaldehyde Tetraethyl- benzo(B)thiophene- diethylene- carboxylate triamine Compound 857 2-Amino-5- 3-(Chloromethyl)- 4-Chloro-3- Diispropanol- fluorobenzoic acid benzoyl chloride trifluoromethyl- amine methyl ester benzaldehyde Compound 858 2-Amino-5- 3-(Chloromethyl)- 3,4-Dimethyl- N,N-Diethyl- piperidine-1-yl- benzoyl chloride benzaldehyde N′-methyl- benzoic acid methyl ethylene- ester diamine Compound 859 2-Amino-5- 3-(Chloromethyl)- p-Tolualdehyde N,N-Diethyl- piperidine-1-yl- benzoyl chloride N′-methyl- benzoic acid methyl ethylene- ester diamine Compound 860 2-Amino-5- 3-(Chloromethyl)- 4-Fluoro- N,N-Diethyl- piperidine-1-yl- benzoyl chloride benzaldehyde N′-methyl- benzoic acid methyl ethylene- ester diamine Compound 861 2-Amino-5- 3-(Chloromethyl)- 3-Fluorobenzaldehyde N,N-Diethyl- piperidine-1-yl- benzoyl chloride N′-methyl- benzoic acid methyl ethylene- ester diamine Compound 862 2-Amino-5- 3-(Chloromethyl)- 4-Chloro-3- N,N-Diethyl- piperidine-1-yl- benzoyl chloride trifluoromethyl- N′-methyl- benzoic acid methyl benzaldehyde ethylene- ester diamine Compound 863 2-Amino-5- 3-(Chloromethyl)- p-Methoxy- N,N-Diethyl- piperidine-1-yl- benzoyl chloride benzaldehyde N′-methyl- benzoic acid methyl ethylene- ester diamine Compound 864 2-Amino-5- 3-(Chloromethyl)- 3,4-Dimethyl- 4-Piperazine- piperidine-1-yl- benzoyl chloride benzaldehyde ethanol benzoic acid methyl ester Compound 865 2-Amino-5- 3-(Chloromethyl)- p-Tolualdehyde 4-Piperazine- piperidine-1-yl- benzoyl chloride ethanol benzoic acid methyl ester Compound 866 2-Amino-5- 3-(Chloromethyl)- 4-Fluorobenzaldehyde 4-Piperazine- piperidine-1-yl- benzoyl chloride ethanol benzoic acid methyl ester Compound 867 2-Amino-5- 3-(Chloromethyl)- 3-Fluorobenzaldehyde 4-Piperazine- piperidine-1-yl- benzoyl chloride ethanol benzoic acid methyl ester Compound 868 2-Amino-5- 3-(Chloromethyl)- 4-Chloro-3- 4-Piperazine- piperidine-1-yl- benzoyl chloride trifluoromethyl- ethanol benzoic acid methyl benzaldehyde ester Compound 869 2-Amino-5- 3-(Chloromethyl)- p-Methoxy- 4-Piperazine- piperidine-1-yl- benzoyl chloride benzaldehyde ethanol benzoic acid methyl ester Compound 870 2-Amino-5- 3-(Chloromethyl)- 3,4-Dimethyl- 4-Hydroxy- piperidine-1-yl- benzoyl chloride benzaldehyde piperidine benzoic acid methyl ester Compound 871 2-Amino-5- 3-(Chloromethyl)- p-Tolualdehyde 4-Hydroxy- piperidine-1-yl- benzoyl chloride piperidine benzoic acid methyl ester Compound 872 2-Amino-5- 3-(Chloromethyl)- 4-Fluorobenzaldehyde 4-Hydroxy- piperidine-1-yl- benzoyl chloride piperidine benzoic acid methyl ester Compound 873 2-Amino-5- 3-(Chloromethyl)- 3-Fluorobenzaldehyde 4-Hydroxy- piperidine-1-yl- benzoyl chloride piperidine benzoic acid methyl ester Compound 874 2-Amino-5- 3-(Chloromethyl)- 4-Chloro-3- 4-Hydroxy- piperidine-1-yl- benzoyl chloride trifluoromethyl- piperidine benzoic acid methyl benzaldehyde ester Compound 875 2-Amino-5- 3-(Chloromethyl)- p-Methoxy- 4-Hydroxy- piperidine-1-yl- benzoyl chloride benzaldehyde piperidine benzoic acid methyl ester Compound 876 2-Amino-5- 3-(Chloromethyl)- 3,4-Dimethyl- 2-(Diethyl- piperidine-1-yl- benzoyl chloride benzaldehyde amino)- benzoic acid methyl ethanethiol ester Compound 877 2-Amino-5- 3-(Chloromethyl)- 4-Fluorobenzaldehyde 2-(Diethyl- piperidine-1-yl- benzoyl chloride amino)- benzoic acid methyl ethanethiol ester Compound 878 2-Amino-5- 3-(Chloromethyl)- 4-Chloro-3- 2-(Diethyl- piperidine-1-yl- benzoyl chloride trifluoromethyl- amino)- benzoic acid methyl benzaldehyde ethanethiol ester Compound 879 2-Amino-5- 3-(Chloromethyl)- p-Methoxybenzaldehyde 2-(Diethyl- piperidine-1-yl- benzoyl chloride amino)- benzoic acid methyl ethanethiol ester Compound 880 2-Amino-5- 3-(Chloromethyl)- 3,4-Dimethyl- 2-Mercapto- piperidine-1-yl- benzoyl chloride benzaldehyde ethanol benzoic acid methyl ester Compound 881 2-Amino-5- 3-(Chloromethyl)- p-Tolualdehyde 2-Mercapto- piperidine-1-yl- benzoyl chloride ethanol benzoic acid methyl ester Compound 882 2-Amino-5- 3-(Chloromethyl)- 4-Fluorobenzaldehyde 2-Mercapto- piperidine-1-yl- benzoyl chloride ethanol benzoic acid methyl ester Compound 883 2-Amino-5- 3-(Chloromethyl)- 3-Fluorobenzaldehyde 2-Mercapto- piperidine-1-yl- benzoyl chloride ethanol benzoic acid methyl ester Compound 884 2-Amino-5- 3-(Chloromethyl)- 4-Chloro-3- 2-Mercapto- piperidine-1-yl- benzoyl chloride trifluoromethyl- ethanol benzoic acid methyl benzaldehyde ester Compound 885 2-Amino-5- 3-(Chloromethyl)- p-Methoxy- 2-Mercapto- piperidine-1-yl- benzoyl chloride benzaldehyde ethanol benzoic acid methyl ester Compound 886 2-Amino-5- 3-(Chloromethyl)- 3,4-Dimethyl- 3-Mercapto- piperidine-1-yl- benzoyl chloride benzaldehyde propionic acid benzoic acid methyl ester Compound 887 2-Amino-5- 3-(Chloromethyl)- p-Tolualdehyde 3-Mercapto- piperidine-1-yl- benzoyl chloride propionic acid benzoic acid methyl ester Compound 888 2-Amino-5- 3-(Chloromethyl)- 4-Fluorobenzaldehyde 3-Mercapto- piperidine-1-yl- benzoyl chloride propionic acid benzoic acid methyl ester Compound 889 2-Amino-5- 3-(Chloromethyl)- 4-Chloro-3- 3-Mercapto- piperidine-1-yl- benzoyl chloride trifluoromethyl- propionic acid benzoic acid methyl benzaldehyde ester Compound 890 2-Amino-5- 3-(Chloromethyl)- p-Methoxy- 3-Mercapto- piperidine-1-yl- benzoyl chloride benzaldehyde propionic acid benzoic acid methyl ester Compound 891 2-Amino-5- 3-(Chloromethyl)- 4-Chloro-3- Mercapto- piperidine-1-yl- benzoyl chloride trifluoromethyl- acetic acid benzoic acid methyl benzaldehyde ester Compound 892 2-Amino-5- 3-(Chloromethyl)- p-Methoxy- Mercapto- piperidine-1-yl- benzoyl chloride benzaldehyde acetic acid benzoic acid methyl ester Compound 893 2-Amino-5- 3-(Chloromethyl)- 3,4-Dimethyl- 1,2,3,4-Tetra- piperidine-1-yl- benzoyl chloride benzaldehyde hydropyrido- benzoic acid methyl [4,3-b][1,8]- ester naphthyridine Compound 894 2-Amino-5- 3-(Chloromethyl)- p-Tolualdehyde 1,2,3,4-Tetra- piperidine-1-yl- benzoyl chloride hydropyrido- benzoic acid methyl [4,3-b][1,8]- ester naphthyridine Compound 895 2-Amino-5- 3-(Chloromethyl)- 4-Fluorobenzaldehyde 1,2,3,4-Tetra- piperidine-1-yl- benzoyl chloride hydropyrido- benzoic acid methyl [4,3-b][1,8]- ester naphthyridine Compound 896 2-Amino-5- 3-(Chloromethyl)- 3-Fluorobenzaldehyde 1,2,3,4-Tetra- piperidine-1-yl- benzoyl chloride hydropyrido- benzoic acid methyl [4,3-b][1,8]- ester naphthyridine Compound 897 2-Amino-5- 3-(Chloromethyl)- 4-Chloro-3- 1,2,3,4-Tetra- piperidine-1-yl- benzoyl chloride trifluoromethyl- hydropyrido- benzoic acid methyl benzaldehyde [4,3-b][1,8]- ester naphthyridine Compound 898 2-Amino-5- 3-(Chloromethyl)- p-Methoxy- 1,2,3,4-Tetra- piperidine-1-yl- benzoyl chloride benzaldehyde hydropyrido- benzoic acid methyl [4,3-b][1,8]- ester naphthyridine Compound 899 2-Amino-5- 3-(Chloromethyl)- 3,4-Dimethyl- 3-Mercapto- piperidine-1-yl- benzoyl chloride benzaldehyde 1,2-propane- benzoic acid methyl diol ester Compound 900 2-Amino-5- 3-(Chloromethyl)- p-Tolualdehyde 3-Mercapto- piperidine-1-yl- benzoyl chloride 1,2-propane- benzoic acid methyl diol ester Compound 901 2-Amino-5- 3-(Chloromethyl)- 4-Fluorobenzaldehyde 3-Mercapto- piperidine-1-yl- benzoyl chloride 1,2-propane- benzoic acid methyl diol ester Compound 902 2-Amino-5- 3-(Chloromethyl)- 3-Fluorobenzaldehyde 3-Mercapto- piperidine-1-yl- benzoyl chloride 1,2-propane- benzoic acid methyl diol ester Compound 903 2-Amino-5- 3-(Chloromethyl)- 4-Chloro-3- 3-Mercapto- piperidine-1-yl- benzoyl chloride trifluoromethyl- 1,2-propane- benzoic acid methyl benzaldehyde diol ester Compound 904 2-Amino-5- 3-(Chloromethyl)- p-Methoxy- 3-Mercapto- piperidine-1-yl- benzoyl chloride benzaldehyde 1,2-propane- benzoic acid methyl diol ester Compound 905 2-Amino-5- 3-(Chloromethyl)- 3,4-Dimethyl- 1,1,7,7- piperidine-1-yl- benzoyl chloride benzaldehyde Tetraethyl- benzoic acid methyl diethylene- ester triamine Compound 906 2-Amino-5- 3-(Chloromethyl)- p-Tolualdehyde 1,1,7,7- piperidine-1-yl- benzoyl chloride Tetraethyl- benzoic acid methyl diethylene- ester triamine Compound 907 2-Amino-5- 3-(Chloromethyl)- 4-Fluorobenzaldehyde 1,1,7,7- piperidine-1-yl- benzoyl chloride Tetraethyl- benzoic acid methyl diethylene- ester triamine Compound 908 2-Amino-5- 3-(Chloromethyl)- 3-Fluorobenzaldehyde 1,1,7,7- piperidine-1-yl- benzoyl chloride Tetraethyl- benzoic acid methyl diethylene- ester triamine Compound 909 2-Amino-5- 3-(Chloromethyl)- 4-Chloro-3- 1,1,7,7- piperidine-1-yl- benzoyl chloride trifluoromethyl- Tetraethyl- benzoic acid methyl benzaldehyde diethylene- ester triamine Compound 910 2-Amino-5- 3-(Chloromethyl)- p-Methoxy- 1,1,7,7- piperidine-1-yl- benzoyl chloride benzaldehyde Tetraethyl- benzoic acid methyl diethylene- ester triamine Compound 911 2-Amino-5- 3-(Chloromethyl)- 4-Chloro-3- N,N-Diethyl- dipropylamino- benzoyl chloride trifluoromethyl- N′-methyl- benzoic acid methyl benzaldehyde ethylene- ester diamine Compound 912 2-Amino-5- 3-(Chloromethyl)- p-Methoxy- N,N-Diethyl- dipropylamino- benzoyl chloride benzaldehyde N′-methyl- benzoic acid methyl ethylene- ester diamine Compound 913 2-Amino-5- 3-(Chloromethyl)- 3,4-Dimethyl- N,N-bis(2- piperidine-1-yl- benzoyl chloride benzaldehyde hydroxyethyl)- benzoic acid methyl ethylene- ester diamine Compound 914 2-Amino-5- 3-(Chloromethyl)- 4-Chloro-3- N,N-bis(2- piperidine-1-yl- benzoyl chloride trifluoromethyl- hydroxyethyl)- benzoic acid methyl benzaldehyde ethylene- ester diamine Compound 915 2-Amino-5- 3-(Chloromethyl)- p-Methoxy- N,N-bis(2- piperidine-1-yl- benzoyl chloride benzaldehyde hydroxyethyl)- benzoic acid methyl ethylene- ester diamine Compound 916 2-Amino-5- 3-(Chloromethyl)- 3,4-Dimethyl- N,N-Diethyl- pyrrolidine-1-yl- benzoyl chloride benzaldehyde N′-methyl- benzoic acid methyl ethylene- ester diamine Compound 917 2-Amino-5- 3-(Chloromethyl)- 4-Chloro-3- N,N-Diethyl- pyrrolidine-1-yl- benzoyl chloride trifluoromethyl- N′-methyl- benzoic acid methyl benzaldehyde ethylene- ester diamine Compound 918 2-Amino-5- 3-(Chloromethyl)- p-Methoxy- N,N-Diethyl- pyrrolidine-1-yl- benzoyl chloride benzaldehyde N′-methyl- benzoic acid methyl ethylene- ester diamine Compound 919 2-Amino-5- 3-(Chloromethyl)- 3,4-Dimethyl- 2-Mercapto- pyrrolidine-1-yl- benzoyl chloride benzaldehyde ethanol benzoic acid methyl ester Compound 920 2-Amino-5- 3-(Chloromethyl)- 4-Chloro-3- 2-Mercapto- pyrrolidine-1-yl- benzoyl chloride trifluoromethyl- ethanol benzoic acid methyl benzaldehyde ester Compound 921 2-Amino-5- 3-(Chloromethyl)- p-Methoxy- 2-Mercapto- pyrrolidine-1-yl- benzoyl chloride benzaldehyde ethanol benzoic acid methyl ester Compound 922 2-Amino-5-(4- 3-(Chloromethyl)- 4-Chloro-3- N,N-Diethyl- methyl- benzoyl chloride trifluoromethyl- N′-methyl [1,4]diazepin-1-yl)- benzaldehyde ethylene- benzoic acid methyl diamine ester Compound 923 2-Amino-5-[4-(2- 3-(Chloromethyl)- 4-Chloro-3- 2-Mercapto- hydroxy-ethyl)- benzoyl chloride trifluoromethyl- ethanol piperazine-1-yl]- benzaldehyde benzoic acid methyl ester Compound 924 2-Amino-5-[4-(2- 3-(Chloromethyl)- 4-Chloro-3- N,N-Diethyl- hydroxy-ethyl)- benzoyl chloride trifluoromethyl- N′-methyl piperazine-1-yl]- benzaldehyde ethylene- benzoic acid methyl diamine ester Compound 925 1-(4-Amino-3- 3-(Chloromethyl)- 4-Chloro-3- 2-Mercapto- methoxycarbonyl- benzoyl chloride trifluoromethyl- ethanol phenyl)-piperidine- benzaldehyde 3-carboxylic acid Compound 926 2-Amino-5- 3-(Chloromethyl)- 3,4-Dimethyl- 2-Mercapto- thiomorpholine-4-yl- benzoyl chloride benzaldehyde ethanol benzoic acid methyl ester Compound 927 2-Amino-5- 3-(Chloromethyl)- 4-Chloro-3- 2-Mercapto- thiomorpholine-4-yl- benzoyl chloride trifluoromethyl- ethanol benzoic acid methyl benzaldehyde ester Compound 928 2-Amino-5- 3-(Chloromethyl)- p-Methoxy- 2-Mercapto- thiomorpholine-4-yl- benzoyl chloride benzaldehyde ethanol benzoic acid methyl ester Compound 929 2-Amino-5- 3-(Chloromethyl)- 4-Chloro-3- N,N-Diethyl- thiomorpholine-4-yl- benzoyl chloride trifluoromethyl- N′-methyl- benzoic acid methyl benzaldehyde ethylene- ester diamine Compound 930 Methyl 2- 3-(Chloromethyl)- p-Methoxy- Dimethyl- aminothiophene-3- benzoyl chloride benzaldehyde amine carboxylate hydrochloride Compound 931 2-Amino-5-(4- 3-(Chloromethyl)- p-Methoxy- N,N-Diethyl- methyl- benzoyl chloride benzaldehyde N′-methyl- [1,4]diazepin-1-yl)- ethylene- benzoic acid methyl diamine ester Compound 932 2-Amino-5-(4- 3-(Chloromethyl)- 4-Chloro-3- 2-Mercapto- methyl- benzoyl chloride trifluoromethyl- ethanol [1,4]diazepin-1-yl)- benzaldehyde benzoic acid methyl ester Compound 933 2-Amino-5-(4- 3-(Chloromethyl)- p-Methoxy- N,N-Diethyl- methyl- benzoyl chloride benzaldehyde N′-methyl- [1,4]diazepin-1-yl)- ethylene- benzoic acid methyl diamine ester Compound 934 1-(4-Amino-3- 3-(Chloromethyl)- 3,4-Dimethyl- 2-Mercapto- methoxycarbonyl- benzoyl chloride benzaldehyde ethanol phenyl)-piperidine- 3-carboxylic acid Compound 935 2-Amino-5- 3,4-Dimethoxy- 3,4-Dimethyl- piperidine-1-yl- benzoyl chloride benzaldehyde benzoic acid ethyl ester Compound 936 2-Amino-5- 3,4-Dimethoxy- Nicotinaldehyde piperidine-1-yl- benzoyl chloride benzoic acid ethyl ester Compound 937 2-Amino-5- 3,4-Dimethoxy- Imidazole-2- piperidine-1-yl- benzoyl chloride carboxaldehyde benzoic acid ethyl ester Compound 938 2-Amino-5- 3,4-Dimethoxy- Vanillin piperidine-1-yl- benzoyl chloride benzoic acid ethyl ester Compound 939 2-Amino-5- 3,4-Dimethoxy- 3,4-Dimethyl- morpholine-4-yl- benzoyl chloride benzaldehyde benzoic acid ethyl ester Compound 940 2-Amino-5- 3,4-Dimethoxy- Vanillin morpholine-4-yl- benzoyl chloride benzoic acid ethyl ester Compound 941 2-Amino-5- 3,4-Dimethoxy- p-Methoxy- morpholine-4-yl- benzoyl chloride benzaldehyde benzoic acid ethyl ester Compound 942 2-Amino-5- 3-(Chloromethyl)- 4-Chloro-3- Diisopropanol- piperidine-1-yl- benzoyl chloride trifluoromethyl- amine benzoic acid ethyl benzaldehyde ester Compound 943 2-Amino-5-hydroxy- 3-(Chloromethyl)- 3,4-Dimethyl- Diisopropanol- benzoic acid methyl benzoyl chloride benzaldehyde amine ester Compound 944 2-Amino-5-(2-oxo- 3-(Chloromethyl)- 3,4-Dimethyl- Diisopropanol- pyrrolidine-1-yl)- benzoyl chloride benzaldehyde amine benzoic acid methyl ester Compound 945 2-Amino-5-(2-oxo- 3-(Chloromethyl)- 4-Chloro-3- Diisopropanol- pyrrolidine-1-yl)- benzoyl chloride trifluoromethyl- amine benzoic acid methyl benzaldehyde ester Compound 946 2-Amino-5-(2-oxo- 3-(Chloromethyl)- p-Methoxybenzaldehyde Diisopropanol- pyrrolidine-1-yl)- benzoyl chloride amine benzoic acid methyl ester Compound 947 2-Amino-5-(2-oxo- 3-(Chloromethyl)- 4-Fluorobenzaldehyde Diisopropanol- pyrrolidine-1-yl)- benzoyl chloride amine benzoic acid methyl ester Compound 948 2-Amino-5-(2-oxo- 3-(Chloromethyl)- p-Tolualdehyde Diisopropanol- pyrrolidine-1-yl)- benzoyl chloride amine benzoic acid methyl ester Compound 949 2-Amino-5-hydroxy- 3-(Chloromethyl)- 3,4-Dimethyl- Diisopropanol- benzoic acid methyl benzoyl chloride benzaldehyde amine ester Compound 950 2-Amino-5-hydroxy- 3-(Chloromethyl)- 4-Chloro-3- Diisopropanol- benzoic acid methyl benzoyl chloride trifluoromethyl- amine ester benzaldehyde Compound 951 2-Amino-5-hydroxy- 3-(Chloromethyl)- 3,4-Dimethyl- Diisopropanol- benzoic acid methyl benzoyl chloride benzaldehyde amine ester Compound 952 2-Amino-5-hydroxy- 3-(Chloromethyl)- 4-Chloro-3- Diisopropanol- benzoic acid methyl benzoyl chloride trifluoromethyl- amine ester benzaldehyde Compound 953 2-Amino-5-hydroxy- 3-(Chloromethyl)- 3,4-Dimethyl- Diisopropanol- benzoic acid methyl benzoyl chloride benzaldehyde amine ester Compound 954 2-Amino-5-hydroxy- 3-(Chloromethyl)- 4-Chloro-3- Diisopropanol- benzoic acid methyl benzoyl chloride trifluoromethyl- amine ester benzaldehyde Compound 955 Methyl 2- 3,4-Dimethoxy- 4-Chloro-3- aminothiophene-3- benzoyl chloride trifluoromethyl- carboxylate benzaldehyde Compound 956 Ethyl 2-amino-4- 3-(Chloromethyl)- 4-Chloro-3- Diethylamine methylthiophene-3- benzoyl chloride trifluoromethyl- carboxylate benzaldehyde Compound 957 Ethyl 2-amino-4- 3-(Chloromethyl)- p-Methoxy- Diethylamine methylthiophene-3- benzoyl chloride benzaldehyde carboxylate Compound 958 2-Amino-5- 3-(Chloromethyl)- p-Methoxy- Diisopropanol- piperidine-1-yl- benzoyl chloride benzaldehyde amine benzoic acid ethyl ester Compound 959 3-Amino- 3-(Chloromethyl)- 3-Fluorobenzaldehyde Diisopropanol- naphthalene-2- benzoyl chloride amine carboxylic acid methyl ester Compound 960 3-Amino- 3-(Chloromethyl)- p-Tolualdehyde Diisopropanol- naphthalene-2- benzoyl chloride amine carboxylic acid methyl ester Compound 961 3-Amino- 3-(Chloromethyl)- 3,4-Dimethyl- Diisopropanol- naphthalene-2- benzoyl chloride benzaldehyde amine carboxylic acid methyl ester Compound 962 3-Amino- 3-(Chloromethyl)- 4-Chloro-3- Diisopropanol- naphthalene-2- benzoyl chloride trifluoromethyl- amine carboxylic acid benzaldehyde methyl ester Compound 963 3-Amino- 3-(Chloromethyl)- p-Methoxy- Diisopropanol- naphthalene-2- benzoyl chloride benzaldehyde amine carboxylic acid methyl ester Compound 964 2-Amino-nicotinoic 3-(Chloromethyl)- 3-Fluorobenzaldehyde Diisopropanol- acid methyl ester benzoyl chloride amine Compound 965 2-Amino-nicotinoic 3-(Chloromethyl)- p-Tolualdehyde Diisopropanol- acid methyl ester benzoyl chloride amine Compound 966 2-Amino-nicotinoic 3-(Chloromethyl)- 3,4-Dimethyl- Diisopropanol- acid methyl ester benzoyl chloride benzaldehyde amine Compound 967 2-Amino-nicotinoic 3-(Chloromethyl)- 4-Chloro-3- Diisopropanol- acid methyl ester benzoyl chloride trifluoromethyl- amine benzaldehyde Compound 968 2-Amino-nicotinoic 3-(Chloromethyl)- p-Methoxy- Diisopropanol- acid methyl ester benzoyl chloride benzaldehyde amine Compound 969 3-Amino- 3-(Chloromethyl)- 3-Fluorobenzaldehyde 1-(2-Hydroxy- naphthalene-2- benzoyl chloride ethyl)- carboxylic acid piperazine methyl ester Compound 970 3-Amino- 3-(Chloromethyl)- p-Tolualdehyde 1-(2-Hydroxy- naphthalene-2- benzoyl chloride ethyl)- carboxylic acid piperazine methyl ester Compound 971 3-Amino- 3-(Chloromethyl)- 3,4-Dimethyl- 1-(2-Hydroxy- naphthalene-2- benzoyl chloride benzaldehyde ethyl)- carboxylic acid piperazine methyl ester Compound 972 3-Amino- 3-(Chloromethyl)- 4-Chloro-3- 1-(2-Hydroxy- naphthalene-2- benzoyl chloride trifluoromethyl- ethyl)- carboxylic acid benzaldehyde piperazine methyl ester Compound 973 3-Amino- 3-(Chloromethyl)- p-Methoxybenzaldehyde 1-(2-Hydroxy- naphthalene-2- benzoyl chloride ethyl)- carboxylic acid piperazine methyl ester Compound 974 4-Amino-thiophene- 3-(Chloromethyl)- 3-Fluorobenzaldehyde Diisopropanol- 3-carboxylic acid benzoyl chloride amine methyl ester Compound 975 4-Amino-thiophene- 3-(Chloromethyl)- m-Tolualdehyde Diisopropanol- 3-carboxylic acid benzoyl chloride amine methyl ester Compound 976 4-Amino-thiophene- 3-(Chloromethyl)- p-Tolualdehyde Diisopropanol- 3-carboxylic acid benzoyl chloride amine methyl ester Compound 977 4-Amino-thiophene- 3-(Chloromethyl)- 3,4-Dimethyl- Diisopropanol- 3-carboxylic acid benzoyl chloride benzaldehyde amine methyl ester Compound 978 4-Amino-thiophene- 3-(Chloromethyl)- 4-Chloro-3- Diisopropanol- 3-carboxylic acid benzoyl chloride trifluoromethyl- amine methyl ester benzaldehyde Compound 979 4-Amino-thiophene- 3-(Chloromethyl)- p-Methoxy- Diisopropanol- 3-carboxylic acid benzoyl chloride benzaldehyde amine methyl ester Compound 980 4-Amino-thiophene- 3-(Chloromethyl)- 3-Fluorobenzaldehyde 1-(2-Hydroxy- 3-carboxylic acid benzoyl chloride ethyl)- methyl ester piperazine Compound 981 4-Amino-thiophene- 3-(Chloromethyl)- p-Tolualdehyde 1-(2-Hydroxy- 3-carboxylic acid benzoyl chloride ethyl)- methyl ester piperazine Compound 982 4-Amino-thiophene- 3-(Chloromethyl)- 3,4-Dimethyl- 1-(2-Hydroxy- 3-carboxylic acid benzoyl chloride benzaldehyde ethyl)- methyl ester piperazine Compound 983 4-Amino-thiophene- 3-(Chloromethyl)- 4-Chloro-3- 1-(2-Hydroxy- 3-carboxylic acid benzoyl chloride trifluoromethyl- ethyl)- methyl ester benzaldehyde piperazine Compound 984 4-Amino-thiophene- 3-(Chloromethyl)- p-Methoxy- 1-(2-Hydroxy- 3-carboxylic acid benzoyl chloride benzaldehyde ethyl)- methyl ester piperazine Compound 985 2-Amino-5- 3-(Chloromethyl)- 3,4-Dimethyl- Diisopropanol- fluorobenzoic acid benzoyl chloride benzaldehyde amine methyl ester Compound 986 2-Amino-5- 3-(Chloromethyl)- 3,4-Dimethyl- Diisopropanol- fluorobenzoic acid benzoyl chloride benzaldehyde amine methyl ester Compound 987 2-Amino-5- 3-(Chloromethyl)- 3-Fluorobenzaldehyde Diisopropanol- fluorobenzoic acid benzoyl chloride amine methyl ester Compound 988 2-Amino-5- 3-(Chloromethyl)- 3-Fluorobenzaldehyde Diisopropanol- fluorobenzoic acid benzoyl chloride amine methyl ester Compound 989 2-Amino-5- 3-(Chloromethyl)- p-Tolualdehyde Diisopropanol- fluorobenzoic acid benzoyl chloride amine methyl ester Compound 990 2-Amino-5- 3-(Chloromethyl)- p-Methoxy- Diisopropanol- fluorobenzoic acid benzoyl chloride benzaldehyde amine methyl ester Compound 991 3-Amino-5-tert- 3-(Chloromethyl)- 3,4-Dimethyl- 1-(2-Hydroxy- butyl-thiophene-2- benzoyl chloride benzaldehyde ethyl)- carboxylic acid piperazine methyl ester Compound 992 3-Amino-thiophene- 3-(Chloromethyl)- 3-Fluorobenzaldehyde Diisopropanol- 2-carboxylic acid benzoyl chloride amine methyl ester Compound 993 3-Amino-thiophene- 3-(Chloromethyl)- 4-Chloro-3-tri- Diisopropanol- 2-carboxylic acid benzoyl chloride fluoromethyl- amine methyl ester benzaldehyde Compound 995 3-Amino-thiophene- 3-(Chloromethyl)- 3-Fluorobenzaldehyde Diethylamine 2-carboxylic acid benzoyl chloride methyl ester Compound 996 Methyl 2-amino-5- 3-(Chloromethyl)- 3-Fluoro- Diisopropanol- bromobenzoate benzoyl chloride acetophenone amine Compound 997 Methyl 2-amino-5- 3-(Chloromethyl)- p-Methoxy Diisopropanol- bromobenzoate benzoyl chloride acetophenone amine Compound 998 Methyl 2-amino-5- 3-(Chloromethyl)- 4-(3-Dimethyl- Diisopropanol- chlorobenzoate benzoyl chloride amino-propoxy)- amine benzaldehyde Compound 999 Methyl 2-amino-5- 3-(Chloromethyl)- 4-(3-Dimethyl- N,N-Diethyl- chlorobenzoate benzoyl chloride amino-propoxy)- N′-methyl- benzaldehyde ethylene- diamine Compound 1000 Methyl 2-amino-5- 3-(Chloromethyl)- (4-Formyl- N,N-Diethyl- chlorobenzoate benzoyl chloride phenoxy)-acetic N′-methyl- acid ethylene- diamine Compound 1001 2-Amino-4,5,6,7- 3-(Chloromethyl)- 4-Trifluoro- N,N-Diethyl- tetrahydro- benzoyl chloride methoxy- N′-methyl- benzothiophene-3- benzaldehyde ethylene- carboxylic acid diamine Compound 1002 2-Amino-4,5,6,7- 3-(Chloromethyl)- 4-(2-Hydroxy- N,N-Diethyl- tetrahydro- benzoyl chloride ethoxy)- N′-methyl- benzothiophene-3- benzaldehyde ethylene- carboxylic acid diamine Compound 1003 2-Amino-4,5,6,7- 3-(Chloromethyl)- 3-Fluoro- N,N-Diethyl- tetrahydro- benzoyl chloride acetophenone N′-methyl- benzothiophene-3- ethylene- carboxylic acid diamine Compound 1004 Methyl 2-amino-5- Quinoxaline-2- 3-Fluorobenzaldehyde chlorobenzoate carbonyl chloride Compound 1005 Methyl 2-amino-5- Quinoxaline-2- 3,4-Dimethyl- chlorobenzoate carbonyl chloride benzaldehyde Compound 1006 Methyl 2-amino-5- Quinoxaline-2- 4-Chloro-3- chlorobenzoate carbonyl chloride trifluoromethyl- benzaldehyde Compound 1007 Methyl 2-amino-5- 3-(Chloromethyl)- 3-Fluorobenzaldehyde 3-Mercapto- chlorobenzoate benzoyl chloride propane-1,2- diol Compound 1008 Methyl 2-amino-5- 3-(Chloromethyl) p-Tolualdehyde 3-Mercapto- chlorobenzoate benzoyl chloride propane-1,2- diol Compound 1009 Methyl 2-amino-5- 3-(Chloromethyl)- 3,4-Dimethyl- 3-Mercapto- chlorobenzoate benzoyl chloride benzaldehyde propane-1,2- diol Compound 1010 Methyl 2-amino-5- 3-(Chloromethyl)- 4-Chloro-3- 3-Mercapto- chlorobenzoate benzoyl chloride trifluoromethyl- propane-1,2- benzaldehyde diol Compound 1011 Methyl 2-amino-5- 3-(Chloromethyl)- p-Methoxy- 3-Mercapto- chlorobenzoate benzoyl chloride benzaldehyde propane-1,2- diol Compound 1012 Methyl 2-amino-5- 3-(Chloromethyl)- 4-Trifluoro- 3-Mercapto- chlorobenzoate benzoyl chloride methoxy- propane-1,2- benzaldehyde diol Compound 1013 2-Amino-4,5-bis-(2- 3-(Chloromethyl)- 3-Fluorobenzaldehyde 3-Mercapto- methoxy-ethoxy)- benzoyl chloride propane-1,2- benzoic acid ethyl diol ester Compound 1014 2-Amino-4,5-bis-(2- 3-(Chloromethyl)- p-Tolualdehyde 3-Mercapto- methoxy-ethoxy)- benzoyl chloride propane-1,2- benzoic acid ethyl diol ester Compound 1015 2-Amino-4,5-bis-(2- 3-(Chloromethyl)- 3,4-Dimethyl- 3-Mercapto- methoxy-ethoxy)- benzoyl chloride benzaldehyde propane-1,2- benzoic acid ethyl diol ester Compound 1016 2-Amino-4,5-bis-(2- 3-(Chloromethyl)- 4-Chloro-3- 3-Mercapto- methoxy-ethoxy)- benzoyl chloride trifluoromethyl- propane-1,2- benzoic acid ethyl benzaldehyde diol ester Compound 1017 2-Amino-5- 3-(Chloromethyl)- 3-Fluorobenzaldehyde 3-Mercapto- methoxy-benzoic benzoyl chloride propane-1,2- acid methyl ester diol Compound 1018 2-Amino-5- 3-(Chloromethyl)- p-Tolualdehyde 3-Mercapto- methoxy-benzoic benzoyl chloride propane-1,2- acid methyl ester diol Compound 1019 2-Amino-5- 3-(Chloromethyl)- 3,4-Dimethyl- 3-Mercapto- methoxy-benzoic benzoyl chloride benzaldehyde propane-1,2- acid methyl ester diol Compound 1020 2-Amino-5- 3-(Chloromethyl)- 4-Chloro-3- 3-Mercapto- methoxy-benzoic benzoyl chloride trifluoromethyl- propane-1,2- acid methyl ester benzaldehyde diol Compound 1021 2-Amino-5- 3-(Chloromethyl)- p-Methoxy- 3-Mercapto- methoxy-benzoic benzoyl chloride benzaldehyde propane-1,2- acid methyl ester diol Compound 1022 2-Amino-5- 3-(Chloromethyl)- 3-Fluorobenzaldehyde N,N-Diethyl- methoxy-benzoic benzoyl chloride N′-methyl- acid methyl ester ethylene- diamine Compound 1023 2-Amino-5- 3-(Chloromethyl)- 4-Chloro-3- N,N-Diethyl- methoxy-benzoic benzoyl chloride trifluoromethyl- N′-methyl- acid methyl ester benzaldehyde ethylene- diamine Compound 1024 2-Amino-5- 3-(Chloromethyl)- p-Methoxy- N,N-Diethyl- methoxy-benzoic benzoyl chloride benzaldehyde N′-methyl- acid methyl ester ethylene- diamine Compound 1025 2-Amino-5- 3-(Chloromethyl)- 3-Fluorobenzaldehyde N,N-Diethyl- methoxy-ethoxy- benzoyl chloride N′-methyl- benzoic acid methyl ethylene- ester diamine Compound 1026 2-Amino-5- 3-(Chloromethyl)- p-Tolualdehyde N,N-Diethyl- methoxy-ethoxy- benzoyl chloride N′-methyl- benzoic acid methyl ethylene- ester diamine Compound 1027 2-Amino-5- 3-(Chloromethyl)- 4-Chloro-3- N,N-Diethyl- methoxy-ethoxy- benzoyl chloride trifluoromethyl- N′-methyl- benzoic acid methyl benzaldehyde ethylene- ester diamine Compound 1028 2-Amino-4,5-bis-(2- 3-(Chloromethyl)- 3-Fluorobenzaldehyde N,N-Diethyl- methoxy-ethoxy)- benzoyl chloride N′-methyl- benzoic acid ethyl ethylene- ester diamine Compound 1029 2-Amino-4,5-bis-(2- 3-(Chloromethyl)- p-Tolualdehyde N,N-Diethyl- methoxy-ethoxy)- benzoyl chloride N′-methyl- benzoic acid ethyl ethylene- ester diamine Compound 1030 2-Amino-4,5-bis-(2- 3-(Chloromethyl)- 3,4-Dimethyl- N,N-Diethyl- methoxy-ethoxy)- benzoyl chloride benzaldehyde N′-methyl- benzoic acid ethyl ethylene- ester diamine Compound 1031 2-Amino-4,5-bis-(2- 3-(Chloromethyl)- 4-Chloro-3- N,N-Diethyl- methoxy-ethoxy)- benzoyl chloride trifluoromethyl- N′-methyl- benzoic acid ethyl benzaldehyde ethylene- ester diamine Compound 1032 2-Amino-4,5-bis-(2- 3-(Chloromethyl)- p-Methoxy- N,N-Diethyl- methoxy-ethoxy)- benzoyl chloride benzaldehyde N′-methyl- benzoic acid ethyl ethylene- ester diamine Compound 1033 2-Amino-5-[2-(2- 3-(Chloromethyl)- 3-Fluorobenzaldehyde N,N-Diethyl- methoxy-ethoxy)- benzoyl chloride N′-methyl- ethoxy]-benzoic ethylene- acid methyl ester diamine Compound 1034 2-Amino-5-[2-(2- 3-(Chloromethyl)- p-Tolualdehyde N,N-Diethyl- methoxy-ethoxy)- benzoyl chloride N′-methyl- ethoxy]-benzoic ethylene- acid methyl ester diamine Compound 1035 2-Amino-5-[2-(2- 3-(Chloromethyl)- 3,4-Dimethyl- N,N-Diethyl- methoxy-ethoxy)- benzoyl chloride benzaldehyde N′-methyl- ethoxy]-benzoic ethylene- acid methyl ester diamine Compound 1036 2-Amino-5-[2-(2- 3-(Chloromethyl)- 4-Chloro-3-tri- N,N-Diethyl- methoxy-ethoxy)- benzoyl chloride fluoromethyl- N′-methyl- ethoxy]-benzoic benzaldehyde ethylene- acid methyl ester diamine Compound 1037 2-Amino-5-[2-(2- 3-(Chloromethyl)- p-Methoxy- N,N-Diethyl- methoxy-ethoxy)- benzoyl chloride benzaldehyde N′-methyl- ethoxy]-benzoic ethylene- acid methyl ester diamine Compound 1038 2-Amino-5-(3- 3-(Chloromethyl)- 4-Chloro-3- N,N-Diethyl- piperidine-1-yl- benzoyl chloride trifluoromethyl- N′-methyl- propoxy)-benzoic benzaldehyde ethylene- acid methyl ester diamine Compound 1039 2-Amino-5-(3- 3-(Chloromethyl)- 4-Chloro-3- 2-Mercapto- piperidine-1-yl- benzoyl chloride trifluoromethyl- ethanol propoxy)-benzoic benzaldehyde acid methyl ester Compound 1040 2-Amino-5-(3- 3-(Chloromethyl)- p-Methoxy- 2-Mercapto- piperidine-1-yl- benzoyl chloride benzaldehyde ethanol propoxy)-benzoic acid methyl ester Compound 1041 2-Amino-5-(3- 3-(Chloromethyl)- 3,4-Dimethyl- 2-Mercapto- piperidine-1-yl- benzoyl chloride benzaldehyde ethanol propoxy)-benzoic acid methyl ester Compound 1042 2-Amino-5-(2- 3-(Chloromethyl)- p-Tolualdehyde 2-Mercapto- piperidine-1-yl- benzoyl chloride ethanol ethoxy)-benzoic acid methyl ester Compound 1043 2-Amino-5-(2- 3-(Chloromethyl)- 3,4-Dimethyl- 2-Mercapto- piperidine-1-yl- benzoyl chloride benzaldehyde ethanol ethoxy)-benzoic acid methyl ester Compound 1044 2-Amino-5-(2- 3-(Chloromethyl)- 4-Chloro-3- 2-Mercapto- piperidine-1-yl- benzoyl chloride trifluoromethyl- ethanol ethoxy)-benzoic benzaldehyde acid methyl ester Compound 1045 2-Amino-5-(2- 3-(Chloromethyl)- p-Methoxy- 2-Mercapto- piperidine-1-yl- benzoyl chloride benzaldehyde ethanol ethoxy)-benzoic acid methyl ester Compound 1046 2-Amino-5- 3-(Chloromethyl)- 3-Fluorobenzaldehyde N,N-Diethyl- cyclohexylmethoxy- benzoyl chloride N′-methyl- benzoic acid methyl ethylene- ester diamine Compound 1047 2-Amino-5- 3-(Chloromethyl)- p-Tolualdehyde N,N-Diethyl- cyclohexylmethoxy- benzoyl chloride N′-methyl- benzoic acid methyl ethylene- ester diamine Compound 1048 2-Amino-5- 3-(Chloromethyl)- 3,4-Dimethyl- N,N-Diethyl- cyclohexylmethoxy- benzoyl chloride benzaldehyde N′-methyl- benzoic acid methyl ethylene- ester diamine Compound 1049 2-Amino-5- 3-(Chloromethyl)- 4-Chloro-3- N,N-Diethyl- cyclohexylmethoxy- benzoyl chloride trifluoromethyl- N′-methyl- benzoic acid methyl benzaldehyde ethylene- ester diamine Compound 1050 2-Amino-5- 3-(Chloromethyl)- p-Methoxy- N,N-Diethyl- cyclohexylmethoxy- benzoyl chloride benzaldehyde N′-methyl- benzoic acid methyl ethylene- ester diamine Compound 1051 2-Amino-5-(4- 3-(Chloromethyl)- 3-Fluorobenzaldehyde 2-Mercapto- fluoro-butoxy)- benzoyl chloride ethanol benzoic acid methyl ester Compound 1052 2-Amino-5-(4- 3-(Chloromethyl)- p-Tolualdehyde 2-Mercapto- fluoro-butoxy)- benzoyl chloride ethanol benzoic acid methyl ester Compound 1053 2-Amino-5-(4- 3-(Chloromethyl)- 3,4-Dimethyl- 2-Mercapto- fluoro-butoxy)- benzoyl chloride benzaldehyde ethanol benzoic acid methyl ester Compound 1054 2-Amino-5-(4- 3-(Chloromethyl)- 4-Chloro-3- 2-Mercapto- fluoro-butoxy)- benzoyl chloride trifluoromethyl- ethanol benzoic acid methyl benzaldehyde ester Compound 1055 2-Amino-5-(4- 3-(Chloromethyl)- p-Methoxy- 2-Mercapto- fluoro-butoxy)- benzoyl chloride benzaldehyde ethanol benzoic acid methyl ester Compound 1056 Ethyl-2-amino- 3-(Chloromethyl)- p-Tolualdehyde 1,1,7,7- 4,5,6,7- benzoyl chloride Tetraethyl- tetrahydrobenzo(B)- diethylene- thiophene-3- triamine carboxylate Compound 1057 2-Amino-5-(4- 3-(Chloromethyl)- 3-Fluorobenzaldehyde N,N-Diethyl- fluoro-butoxy)- benzoyl chloride N′-methyl- benzoic acid methyl ethylene- ester diamine Compound 1058 2-Amino-5-(4- 3-(Chloromethyl)- p-Tolualdehyde N,N-Diethyl- fluoro-butoxy)- benzoyl chloride N′-methyl- benzoic acid methyl ethylene- ester diamine Compound 1059 2-Amino-5-(4- 3-(Chloromethyl)- 3,4-Dimethyl- N,N-Diethyl- fluoro-butoxy)- benzoyl chloride benzaldehyde N′-methyl- benzoic acid methyl ethylene- ester diamine Compound 1060 2-Amino-5-(4- 3-(Chloromethyl)- 4-Chloro-3- N,N-Diethyl- fluoro-butoxy)- benzoyl chloride trifluoromethyl- N′-methyl- benzoic acid methyl benzaldehyde ethylene- ester diamine Compound 1061 2-Amino-5-(4- 3-(Chloromethyl)- p-Methoxy- N,N-Diethyl- fluoro-butoxy)- benzoyl chloride benzaldehyde N′-methyl- benzoic acid methyl ethylene- ester diamine Compound 1062 2-Amino-5-(4- 3-(Chloromethyl)- 3-Trifluoro- 2-Mercapto- Hydroxypiperidine- benzoyl chloride methyl-4-chloro- ethanol 1-yl)-benzoic acid benzaldehyde methyl ester Compound 1063 2-Amino-5-(4- 3-(Chloromethyl)- 3-Trifluoro- 2-Mercapto- hydroxymethyl- benzoyl chloride methyl-4-chloro- ethanol piperidine-1-yl)- benzaldehyde benzoic acid methyl ester Compound 1064 2-Amino-5- 3-(Chloromethyl)- 3,4-Dimethyl- 2-Mercapto- morpholine-4-yl- benzoyl chloride benzaldehyde ethanol benzoic acid methyl ester Compound 1065 2-Amino-5- 3-(Chloromethyl)- 3-Trifluoro- 2-Mercapto- morpholine-4-yl- benzoyl chloride methyl-4-chloro- ethanol benzoic acid methyl benzaldehyde ester Compound 1066 2-Amino-5- 3-(Chloromethyl)- p-Methoxy- 2-Mercapto- morpholine-4-yl- benzoyl chloride benzaldehyde ethanol benzoic acid methyl ester Compound 1067 2-Amino-5- 3-(Chloromethyl)- 3-Trifluoro- 2-Mercapto- [1,4′]bipiperidinyl-1′- benzoyl chloride methyl-4-chloro- ethanol yl-benzoic acid benzaldehyde methyl ester Compound 1068 2-Amino-5- 3-(Chloromethyl)- p-Methoxy- 2-Mercapto- [1,4′]bipiperidinyl-1′- benzoyl chloride benzaldehyde ethanol yl-benzoic acid methyl ester Compound 1069 2-Amino-5-(4- 3-(Chloromethyl)- 3,4-Dimethyl- 2-Mercapto- methyl-piperidine-1- benzoyl chloride benzaldehyde ethanol yl)-benzoic acid methyl ester Compound 1070 2-Amino-5-(4- 3-(Chloromethyl)- 3-Trifluoro- 2-Mercapto- methyl-piperidine-1- benzoyl chloride methyl-4-chloro- ethanol yl)-benzoic acid benzaldehyde methyl ester Compound 1071 2-Amino-5-(4- 3-(Chloromethyl)- p-Methoxy- 2-Mercapto- methyl-piperidine-1- benzoyl chloride benzaldehyde ethanol yl)-benzoic acid methyl ester Compound 1072 2-Amino-5-(4- 3-(Chloromethyl)- 3-Trifluoro- 2-Mercapto- methyl-piperazine- benzoyl chloride methyl-4-chloro- ethanol 1-yl)-benzoic acid benzaldehyde methyl ester Compound 1073 2-Amino-5-(4- 3-(Chloromethyl)- p-Methoxy- 2-Mercapto- methyl-piperazine- benzoyl chloride benzaldehyde ethanol 1-yl)-benzoic acid methyl ester Compound 1074 2-Amino-5- 3-(Chloromethyl)- 3,4-Dimethyl- N,N-Diethyl- morpholine-4-yl- benzoyl chloride benzaldehyde N′-methyl- benzoic acid methyl ethylene- ester diamine Compound 1075 2-Amino-5- 3-(Chloromethyl)- 3-Trifluoro- N,N-Diethyl- morpholine-4-yl- benzoyl chloride methyl-4-chloro- N′-methyl- benzoic acid methyl benzaldehyde ethylene- ester diamine Compound 1076 2-Amino-5- 3-(Chloromethyl)- p-Methoxy- N,N-Diethyl- morpholine-4-yl- benzoyl chloride benzaldehyde N′-methyl- benzoic acid methyl ethylene- ester diamine

Starting compounds and reaction paths used in the synthesis of compounds corresponding to compounds A in synthesizing compounds 853, 854, 857 to 929, 931 to 942, 944 to 948, 958 to 973, 985 to 990, 1013 to 1055, and 1057 to 1076 are shown in Table 2. In the table, compounds A′, D, and E correspond to compounds described in Examples and schemes A to H.

TABLE 2 A′ D E Reaction path Compound 853 2-Amino-5- Scheme G fluorobenzoic acid Compound 854 2-Amino-5- Scheme G fluorobenzoic acid Compound 857 2-Amino-5- Scheme G fluorobenzoic acid Compound 858 5-Chloro-2-nitro- Piperidine Scheme A benzoic acid Compound 859 5-Chloro-2-nitro- Piperidine Scheme A benzoic acid Compound 860 5-Chloro-2-nitro- Piperidine Scheme A benzoic acid Compound 861 5-Chloro-2-nitro- Piperidine Scheme A benzoic acid Compound 862 5-Chloro-2-nitro- Piperidine Scheme A benzoic acid Compound 863 5-Chloro-2-nitro- Piperidine Scheme A benzoic acid Compound 864 5-Chloro-2-nitro- Piperidine Scheme A benzoic acid Compound 865 5-Chloro-2-nitro- Piperidine Scheme A benzoic acid Compound 866 5-Chloro-2-nitro- Piperidine Scheme A benzoic acid Compound 867 5-Chloro-2-nitro- Piperidine Scheme A benzoic acid Compound 868 5-Chloro-2-nitro- Piperidine Scheme A benzoic acid Compound 869 5-Chloro-2-nitro- Piperidine Scheme A benzoic acid Compound 870 5-Chloro-2-nitro- Piperidine Scheme A benzoic acid Compound 871 5-Chloro-2-nitro- Piperidine Scheme A benzoic acid Compound 872 5-Chloro-2-nitro- Piperidine Scheme A benzoic acid Compound 873 5-Chloro-2-nitro- Piperidine Scheme A benzoic acid Compound 874 5-Chloro-2-nitro- Piperidine Scheme A benzoic acid Compound 875 5-Chloro-2-nitro- Piperidine Scheme A benzoic acid Compound 876 5-Chloro-2-nitro- Piperidine Scheme A benzoic acid Compound 877 5-Chloro-2-nitro- Piperidine Scheme A benzoic acid Compound 878 5-Chloro-2-nitro- Piperidine Scheme A benzoic acid Compound 879 5-Chloro-2-nitro- Piperidine Scheme A benzoic acid Compound 880 5-Chloro-2-nitro- Piperidine Scheme A benzoic acid Compound 881 5-Chloro-2-nitro- Piperidine Scheme A benzoic acid Compound 882 5-Chloro-2-nitro- Piperidine Scheme A benzoic acid Compound 883 5-Chloro-2-nitro- Piperidine Scheme A benzoic acid Compound 884 5-Chloro-2-nitro- Piperidine Scheme A benzoic acid Compound 885 5-Chloro-2-nitro- Piperidine Scheme A benzoic acid Compound 886 5-Chloro-2-nitro- Piperidine Scheme A benzoic acid Compound 887 5-Chloro-2-nitro- Piperidine Scheme A benzoic acid Compound 888 5-Chloro-2-nitro- Piperidine Scheme A benzoic acid Compound 889 5-Chloro-2-nitro- Piperidine Scheme A benzoic acid Compound 890 5-Chloro-2-nitro- Piperidine Scheme A benzoic acid Compound 891 5-Chloro-2-nitro- Piperidine Scheme A benzoic acid Compound 892 5-Chloro-2-nitro- Piperidine Scheme A benzoic acid Compound 893 5-Chloro-2-nitro- Piperidine Scheme A benzoic acid Compound 894 5-Chloro-2-nitro- Piperidine Scheme A benzoic acid Compound 895 5-Chloro-2-nitro- Piperidine Scheme A benzoic acid Compound 896 5-Chloro-2-nitro- Piperidine Scheme A benzoic acid Compound 897 5-Chloro-2-nitro- Piperidine Scheme A benzoic acid Compound 898 5-Chloro-2-nitro- Piperidine Scheme A benzoic acid Compound 899 5-Chloro-2-nitro- Piperidine Scheme A benzoic acid Compound 900 5-Chloro-2-nitro- Piperidine Scheme A benzoic acid Compound 901 5-Chloro-2-nitro- Piperidine Scheme A benzoic acid Compound 902 5-Chloro-2-nitro- Piperidine Scheme A benzoic acid Compound 903 5-Chloro-2-nitro- Piperidine Scheme A benzoic acid Compound 904 5-Chloro-2-nitro- Piperidine Scheme A benzoic acid Compound 905 5-Chloro-2-nitro- Piperidine Scheme A benzoic acid Compound 906 5-Chloro-2-nitro- Piperidine Scheme A benzoic acid Compound 907 5-Chloro-2-nitro- Piperidine Scheme A benzoic acid Compound 908 5-Chloro-2-nitro- Piperidine Scheme A benzoic acid Compound 909 5-Chloro-2-nitro- Piperidine Scheme A benzoic acid Compound 910 5-Chloro-2-nitro- Piperidine Scheme A benzoic acid Compound 911 5-Amino-2-nitro- Propionaldehyde Scheme H benzoic acid methyl ester Compound 912 5-Amino-2-nitro- Propionaldehyde Scheme H benzoic acid methyl ester Compound 913 5-Chloro-2-nitro- Piperidine Scheme A benzoic acid Compound 914 5-Chloro-2-nitro- Piperidine Scheme A benzoic acid Compound 915 5-Chloro-2-nitro- Piperidine Scheme A benzoic acid Compound 916 5-Chloro-2-nitro- Pyrrolidine Scheme A benzoic acid Compound 917 5-Chloro-2-nitro- Pyrrolidine Scheme A benzoic acid Compound 918 5-Chloro-2-nitro- Pyrrolidine Scheme A benzoic acid Compound 919 5-Chloro-2-nitro- Pyrrolidine Scheme A benzoic acid Compound 920 5-Chloro-2-nitro- Pyrrolidine Scheme A benzoic acid Compound 921 5-Chloro-2-nitro- Pyrrolidine Scheme A benzoic acid Compound 922 5-Chloro-2-nitro- 1-Methyl- Scheme A benzoic acid homopiperazine Compound 923 5-Chloro-2-nitro- 1-Piperazineethanol Scheme A benzoic acid Compound 924 5-Chloro-2-nitro- 1-Piperazineethanol Scheme A benzoic acid Compound 925 5-Chloro-2-nitro- 3-Piperidine- Scheme A benzoic acid carboxylic acid Compound 926 5-Chloro-2-nitro- Thiomorpholine Scheme A benzoic acid Compound 927 5-Chloro-2-nitro- Thiomorpholine Scheme A benzoic acid Compound 928 5-Chloro-2-nitro- Thiomorpholine Scheme A benzoic acid Compound 929 5-Chloro-2-nitro- Thiomorpholine Scheme A benzoic acid Compound 931 5-Chloro-2-nitro- 1-Methyl- Scheme A benzoic acid homopiperazine Compound 932 5-Chloro-2-nitro- 1-Methyl- Scheme A benzoic acid homopiperazine Compound 933 5-Chloro-2-nitro- 1-Methyl- Scheme A benzoic acid homopiperazine Compound 934 5-Chloro-2-nitro- 3-Piperidine- Scheme A benzoic acid carboxylic acid Compound 935 5-Chloro-2-nitro- Piperidine Scheme A benzoic acid Compound 936 5-Chloro-2-nitro- Piperidine Scheme A benzoic acid Compound 937 5-Chloro-2-nitro- Piperidine Scheme A benzoic acid Compound 938 5-Chloro-2-nitro- Piperidine Scheme A benzoic acid Compound 939 5-Chloro-2-nitro- Morpholine Scheme A benzoic acid Compound 940 5-Chloro-2-nitro- Morpholine Scheme A benzoic acid Compound 941 5-Chloro-2-nitro- Morpholine Scheme A benzoic acid Compound 942 5-Chloro-2-nitro- Piperidine Scheme A benzoic acid Compound 944 5-Amino-2-nitro- 4-Chloro-butyryl Scheme D benzoic acid chloride Compound 945 5-Amino-2-nitro- 4-Chloro-butyryl Scheme D benzoic acid chloride Compound 946 5-Amino-2-nitro- 4-Chloro-butyryl Scheme D benzoic acid chloride Compound 947 5-Amino-2-nitro- 4-Chloro-butyryl Scheme D benzoic acid chloride Compound 948 5-Amino-2-nitro- 4-Chloro-butyryl Scheme D benzoic acid chloride Compound 958 5-Chloro-2-nitro- Piperidine Scheme A benzoic acid Compound 959 3-Amino- Scheme G naphthalene-2- carboxylic acid Compound 960 3-Amino- Scheme G naphthalene-2- carboxylic acid Compound 961 3-Amino- Scheme G naphthalene-2- carboxylic acid Compound 962 3-Amino- Scheme G naphthalene-2- carboxylic acid Compound 963 3-Amino- Scheme G naphthalene-2- carboxylic acid Compound 964 2-Amino-nicotinoic Scheme G acid Compound 965 2-Amino-nicotinoic Scheme G acid Compound 966 2-Amino-nicotinoic Scheme G acid Compound 967 2-Amino-nicotinoic Scheme G acid Compound 968 2-Amino-nicotinoic Scheme G acid Compound 969 3-Amino- Scheme G naphthalene-2- carboxylic acid Compound 970 3-Amino- Scheme G naphthalene-2- carboxylic acid Compound 971 3-Amino- Scheme G naphthalene-2- carboxylic acid Compound 972 3-Amino- Scheme G naphthalene-2- carboxylic acid Compound 973 3-Amino- Scheme G naphthalene-2- carboxylic acid Compound 985 2-Amino-5-fluoro- Scheme G benzoic acid Compound 986 2-Amino-5-fluoro- Scheme G benzoic acid Compound 987 2-Amino-5-fluoro- Scheme G benzoic acid Compound 988 2-Amino-5-fluoro- Scheme G benzoic acid Compound 989 2-Amino-5-fluoro- Scheme G benzoic acid Compound 990 2-Amino-5-fluoro- Scheme G benzoic acid Compound 1013 3,4-Dihydroxy- 1-Bromo-2- Scheme F benzoic acid ethyl methoxy-ethane ester Compound 1014 3,4-Dihydroxy- 1-Bromo-2- Scheme F benzoic acid ethyl methoxy-ethane ester Compound 1015 3,4-Dihydroxy- 1-Bromo-2- Scheme F benzoic acid ethyl methoxy-ethane ester Compound 1016 3,4-Dihydroxy- 1-Bromo-2- Scheme F benzoic acid ethyl methoxy-ethane ester Compound 1017 5-Methoxy-2-nitro- Scheme E benzoic acid Compound 1018 5-Methoxy-2-nitro- Scheme E benzoic acid Compound 1019 5-Methoxy-2-nitro- Scheme E benzoic acid Compound 1020 5-Methoxy-2-nitro- Scheme E benzoic acid Compound 1021 5-Methoxy-2-nitro- Scheme E benzoic acid Compound 1022 5-Methoxy-2-nitro- Scheme E benzoic acid Compound 1023 5-Methoxy-2-nitro- Scheme E benzoic acid Compound 1024 5-Methoxy-2-nitro- Scheme E benzoic acid Compound 1025 5-Hydroxy-2-nitro- 1-Bromo-2- Scheme B benzoic acid methoxy-ethane Compound 1026 5-Hydroxy-2-nitro- 1-Bromo-2- Scheme B benzoic acid methoxy-ethane Compound 1027 5-Hydroxy-2-nitro- 1-Bromo-2- Scheme B benzoic acid methoxy-ethane Compound 1028 3,4-Dihydroxy- 1-Bromo-2- Scheme F benzoic acid ethyl methoxy-ethane ester Compound 1029 3,4-Dihydroxy- 1-Bromo-2- Scheme F benzoic acid ethyl methoxy-ethane ester Compound 1030 3,4-Dihydroxy- 1-Bromo-2- Scheme F benzoic acid ethyl methoxy-ethane ester Compound 1031 3,4-Dihydroxy- 1-Bromo-2- Scheme F benzoic acid ethyl methoxy-ethane ester Compound 1032 3,4-Dihydroxy- 1-Bromo-2- Scheme F benzoic acid ethyl methoxy-ethane ester Compound 1033 5-Hydroxy-2-nitro- 1-Bromo-2-(2- Scheme B benzoic acid methoxy-ethoxy)- ethane Compound 1034 5-Hydroxy-2-nitro- 1-Bromo-2-(2- Scheme B benzoic acid methoxy-ethoxy)- ethane Compound 1035 5-Hydroxy-2-nitro- 1-Bromo-2-(2- Scheme B benzoic acid methoxy-ethoxy)- ethane Compound 1036 5-Hydroxy-2-nitro- 1-Bromo-2-(2- Scheme B benzoic acid methoxy-ethoxy)- ethane Compound 1037 5-Hydroxy-2-nitro- 1-Bromo-2-(2- Scheme B benzoic acid methoxy-ethoxy)- ethane Compound 1038 5-Hydroxy-2-nitro- 1-Bromo-3- Piperidine Scheme C benzoic acid chloropropane Compound 1039 5-Hydroxy-2-nitro- 1-Bromo-3- Piperidine Scheme C benzoic acid chloropropane Compound 1040 5-Hydroxy-2-nitro- 1-Bromo-3- Piperidine Scheme C benzoic acid chloropropane Compound 1041 5-Hydroxy-2-nitro- 1-Bromo-3- Piperidine Scheme C benzoic acid chloropropane Compound 1042 5-Hydroxy-2-nitro- 1-Bromo-2- Piperidine Scheme C benzoic acid chloroethane Compound 1043 5-Hydroxy-2-nitro- 1-Bromo-2- Piperidine Scheme C benzoic acid chloroethane Compound 1044 5-Hydroxy-2-nitro- 1-Bromo-2- Piperidine Scheme C benzoic acid chloroethane Compound 1045 5-Hydroxy-2-nitro- 1-Bromo-2- Piperidine Scheme C benzoic acid chloroethane Compound 1046 5-Hydroxy-2-nitro- Bromomethyl- Scheme B benzoic acid cyclohexane Compound 1047 5-Hydroxy-2-nitro- Bromomethyl- Scheme B benzoic acid cyclohexane Compound 1048 5-Hydroxy-2-nitro- Bromomethyl- Scheme B benzoic acid cyclohexane Compound 1049 5-Hydroxy-2-nitro- Bromomethyl- Scheme B benzoic acid cyclohexane Compound 1050 5-Hydroxy-2-nitro- Bromomethyl- Scheme B benzoic acid cyclohexane Compound 1051 5-Hydroxy-2-nitro- 1-Bromo-4-fluoro- Scheme B benzoic acid butane Compound 1052 5-Hydroxy-2-nitro- 1-Bromo-4-fluoro- Scheme B benzoic acid butane Compound 1053 5-Hydroxy-2-nitro- 1-Bromo-4-fluoro- Scheme B benzoic acid butane Compound 1054 5-Hydroxy-2-nitro- 1-Bromo-4-fluoro- Scheme B benzoic acid butane Compound 1055 5-Hydroxy-2-nitro- 1-Bromo-4-fluoro- Scheme B benzoic acid butane Compound 1057 5-Hydroxy-2-nitro- 1-Bromo-4-fluoro- Scheme B benzoic acid butane Compound 1058 5-Hydroxy-2-nitro- 1-Bromo-4-fluoro- Scheme B benzoic acid butane Compound 1059 5-Hydroxy-2-nitro- 1-Bromo-4-fluoro- Scheme B benzoic acid butane Compound 1060 5-Hydroxy-2-nitro- 1-Bromo-4-fluoro- Scheme B benzoic acid butane Compound 1061 5-Hydroxy-2-nitro 1-Bromo-4-fluoro- Scheme B benzoic acid butane Compound 1062 5-Chloro-2-nitro- 4-Hydroxy- Scheme A benzoic acid piperidine Compound 1063 5-Chloro-2-nitro- 4-Piperidine- Scheme A benzoic acid methanol Compound 1064 5-Chloro-2-nitro- Morpholine Scheme A benzoic acid Compound 1065 5-Chloro-2-nitro- Morpholine Scheme A benzoic acid Compound 1066 5-Chloro-2-nitro- Morpholine Scheme A benzoic acid Compound 1067 5-Chloro-2-nitro- 4-Piperidino- Scheme A benzoic acid piperidine Compound 1068 5-Chloro-2-nitro- 4-Piperidino- Scheme A benzoic acid piperidine Compound 1069 5-Chloro-2-nitro- 4-Methylpiperidine Scheme A benzoic acid Compound 1070 5-Chloro-2-nitro- 4-Methylpiperidine Scheme A benzoic acid Compound 1071 5-Chloro-2-nitro- 4-Methylpiperidine Scheme A benzoic acid Compound 1072 5-Chloro-2-nitro- 4-Methylpiperazine Scheme A benzoic acid Compound 1073 5-Chloro-2-nitro- 4-Methylpiperazine Scheme A benzoic acid Compound 1074 5-Chloro-2-nitro- Morpholine Scheme A benzoic acid Compound 1075 5-Chloro-2-nitro- Morpholine Scheme A benzoic acid Compound 1076 5-Chloro-2-nitro- Morpholine Scheme A benzoic acid Compound 935 5-Chloro-2-nitro- Piperidine Scheme A benzoic acid Compound 936 5-Chloro-2-nitro- Piperidine Scheme A benzoic acid Compound 937 5-Chloro-2-nitro- Piperidine Scheme A benzoic acid Compound 938 5-Chloro-2-nitro- Piperidine Scheme A benzoic acid Compound 939 5-Chloro-2-nitro- Morpholine Scheme A benzoic acid Compound 940 5-Chloro-2-nitro- Morpholine Scheme A benzoic acid Compound 941 5-Chloro-2-nitro- Morpholine Scheme A benzoic acid Compound 942 5-Chloro-2-nitro- Piperidine Scheme A benzoic acid Compound 944 5-Amino-2-nitro- 4-Chloro-butyryl Scheme D benzoic acid chloride Compound 945 5-Amino-2-nitro- 4-Chloro-butyryl Scheme D benzoic acid chloride Compound 946 5-Amino-2-nitro- 4-Chloro-butyryl Scheme D benzoic acid chloride Compound 947 5-Amino-2-nitro- 4-Chloro-butyryl Scheme D benzoic acid chloride Compound 948 5-Amino-2-nitro- 4-Chloro-butyryl Scheme D benzoic acid chloride Compound 958 5-Chloro-2-nitro- Piperidine Scheme A benzoic acid Compound 959 3-Amino- Scheme G naphthalene-2- carboxylic acid Compound 960 3-Amino- Scheme G naphthalene-2- carboxylic acid Compound 961 3-Amino- Scheme G naphthalene-2- carboxylic acid Compound 962 3-Amino- Scheme G naphthalene-2- carboxylic acid Compound 963 3-Amino- Scheme G naphthalene-2- carboxylic acid Compound 964 2-Amino-nicotinoic Scheme G acid Compound 965 2-Amino-nicotinoic Scheme G acid Compound 966 2-Amino-nicotinoic Scheme G acid Compound 967 2-Amino-nicotinoic Scheme G acid Compound 968 2-Amino-nicotinoic Scheme G acid Compound 969 3-Amino- Scheme G naphthalene-2- carboxylic acid Compound 970 3-Amino- Scheme G naphthalene-2- carboxylic acid Compound 971 3-Amino- Scheme G naphthalene-2- carboxylic acid Compound 972 3-Amino- Scheme G naphthalene-2- carboxylic acid Compound 973 3-Amino- Scheme G naphthalene-2- carboxylic acid Compound 985 2-Amino-5-fluoro- Scheme G benzoic acid Compound 986 2-Amino-5-fluoro- Scheme G benzoic acid Compound 987 2-Amino-5-fluoro- Scheme G benzoic acid Compound 988 2-Amino-5-fluoro- Scheme G benzoic acid Compound 989 2-Amino-5-fluoro- Scheme G benzoic acid Compound 990 2-Amino-5-fluoro- Scheme G benzoic acid Compound 1013 3,4-Dihydroxy- 1-Bromo-2- Scheme F benzoic acid ethyl methoxy-ethane ester Compound 1014 3,4-Dihydroxy- 1-Bromo-2- Scheme F benzoic acid ethyl methoxy-ethane ester Compound 1015 3,4-Dihydroxy- 1-Bromo-2- Scheme F benzoic acid ethyl methoxy-ethane ester Compound 1016 3,4-Dihydroxy- 1-Bromo-2- Scheme F benzoic acid ethyl methoxy-ethane ester Compound 1017 5-Methoxy-2-nitro- Scheme E benzoic acid Compound 1018 5-Methoxy-2-nitro- Scheme E benzoic acid Compound 1019 5-Methoxy-2-nitro- Scheme E benzoic acid Compound 1020 5-Methoxy-2-nitro- Scheme E benzoic acid Compound 1021 5-Methoxy-2-nitro- Scheme E benzoic acid Compound 1022 5-Methoxy-2-nitro- Scheme E benzoic acid Compound 1023 5-Methoxy-2-nitro- Scheme E benzoic acid Compound 1024 5-Methoxy-2-nitro- Scheme E benzoic acid Compound 1025 5-Hydroxy-2-nitro- 1-Bromo-2- Scheme B benzoic acid methoxy-ethane Compound 1026 5-Hydroxy-2-nitro- 1-Bromo-2- Scheme B benzoic acid methoxy-ethane Compound 1027 5-Hydroxy-2-nitro- 1-Bromo-2- Scheme B benzoic acid methoxy-ethane Compound 1028 3,4-Dihydroxy- 1-Bromo-2- Scheme F benzoic acid ethyl methoxy-ethane ester Compound 1029 3,4-Dihydroxy- 1-Bromo-2- Scheme F benzoic acid ethyl methoxy-ethane ester Compound 1030 3,4-Dihydroxy- 1-Bromo-2- Scheme F benzoic acid ethyl methoxy-ethane ester Compound 1031 3,4-Dihydroxy- 1-Bromo-2- Scheme F benzoic acid ethyl methoxy-ethane ester Compound 1032 3,4-Dihydroxy- 1-Bromo-2- Scheme F benzoic acid ethyl methoxy-ethane ester Compound 1033 5-Hydroxy-2-nitro- 1-Bromo-2-(2- Scheme B benzoic acid methoxy-ethoxy)- ethane Compound 1034 5-Hydroxy-2-nitro- 1-Bromo-2-(2- Scheme B benzoic acid methoxy-ethoxy)- ethane Compound 1035 5-Hydroxy-2-nitro- 1-Bromo-2-(2- Scheme B benzoic acid methoxy-ethoxy)- ethane Compound 1036 5-Hydroxy-2-nitro- 1-Bromo-2-(2- Scheme B benzoic acid methoxy-ethoxy)- ethane Compound 1037 5-Hydroxy-2-nitro- 1-Bromo-2-(2- Scheme B benzoic acid methoxy-ethoxy)- ethane Compound 1038 5-Hydroxy-2-nitro- 1-Bromo-3- Piperidine Scheme C benzoic acid chloropropane Compound 1039 5-Hydroxy-2-nitro- 1-Bromo-3- Piperidine Scheme C benzoic acid chloropropane Compound 1040 5-Hydroxy-2-nitro- 1-Bromo-3- Piperidine Scheme C benzoic acid chloropropane Compound 1041 5-Hydroxy-2-nitro- 1-Bromo-3- Piperidine Scheme C benzoic acid chloropropane Compound 1042 5-Hydroxy-2-nitro- 1-Bromo-2- Piperidine Scheme C benzoic acid chloroethane Compound 1043 5-Hydroxy-2-nitro- 1-Bromo-2- Piperidine Scheme C benzoic acid chloroethane Compound 1044 5-Hydroxy-2-nitro- 1-Bromo-2- Piperidine Scheme C benzoic acid chloroethane Compound 1045 5-Hydroxy-2-nitro- 1-Bromo-2- Piperidine Scheme C benzoic acid chloroethane Compound 1046 5-Hydroxy-2-nitro- Bromomethyl- Scheme B benzoic acid cyclohexane Compound 1047 5-Hydroxy-2-nitro- Bromomethyl- Scheme B benzoic acid cyclohexane Compound 1048 5-Hydroxy-2-nitro- Bromomethyl- Scheme B benzoic acid cyclohexane Compound 1049 5-Hydroxy-2-nitro- Bromomethyl- Scheme B benzoic acid cyclohexane Compound 1050 5-Hydroxy-2-nitro- Bromomethyl- Scheme B benzoic acid cyclohexane Compound 1051 5-Hydroxy-2-nitro- 1-Bromo-4-fluoro- Scheme B benzoic acid butane Compound 1052 5-Hydroxy-2-nitro- 1-Bromo-4-fluoro- Scheme B benzoic acid butane Compound 1053 5-Hydroxy-2-nitro- 1-Bromo-4-fluoro- Scheme B benzoic acid butane Compound 1054 5-Hydroxy-2-nitro- 1-Bromo-4-fluoro- Scheme B benzoic acid butane Compound 1055 5-Hydroxy-2-nitro- 1-Bromo-4-fluoro- Scheme B benzoic acid butane Compound 1057 5-Hydroxy-2-nitro- 1-Bromo-4-fluoro- Scheme B benzoic acid butane Compound 1058 5-Hydroxy-2-nitro- 1-Bromo-4-fluoro- Scheme B benzoic acid butane Compound 1059 5-Hydroxy-2-nitro- 1-Bromo-4-fluoro- Scheme B benzoic acid butane Compound 1060 5-Hydroxy-2-nitro- 1-Bromo-4-fluoro- Scheme B benzoic acid butane Compound 1061 5-Hydroxy-2-nitro- 1-Bromo-4-fluoro- Scheme B benzoic acid butane Compound 1062 5-Chloro-2-nitro- 4-Hydroxy- Scheme A benzoic acid piperidine Compound 1063 5-Chloro-2-nitro- 4-Piperidine- Scheme A benzoic acid methanol Compound 1064 5-Chloro-2-nitro- Morpholine Scheme A benzoic acid Compound 1065 5-Chloro-2-nitro- Morpholine Scheme A benzoic acid Compound 1066 5-Chloro-2-nitro- Morpholine Scheme A benzoic acid Compound 1067 5-Chloro-2-nitro- 4-Piperidino- Scheme A benzoic acid piperidine Compound 1068 5-Chloro-2-nitro- 4-Piperidino- Scheme A benzoic acid piperidine Compound 1069 5-Chloro-2-nitro- 4-Methylpiperidine Scheme A benzoic acid Compound 1070 5-Chloro-2-nitro- 4-Methylpiperidine Scheme A benzoic acid Compound 1071 5-Chloro-2-nitro- 4-Methylpiperidine Scheme A benzoic acid Compound 1072 5-Chloro-2-nitro- 4-Methylpiperazine Scheme A benzoic acid Compound 1073 5-Chloro-2-nitro- 4-Methylpiperazine Scheme A benzoic acid Compound 1074 5-Chloro-2-nitro- Morpholine Scheme A benzoic acid Compound 1075 5-Chloro-2-nitro- Morpholine Scheme A benzoic acid Compound 1076 5-Chloro-2-nitro- Morpholine Scheme A benzoic acid

Structures of compounds 1 to 1077 are shown in Table 3.

TABLE 3 Compound No. Chemical structural formula Compound 1

Compound 2

Compound 3

Compound 4

Compound 5

Compound 6

Compound 7

Compound 8

Compound 9

Compound 10

Compound 11

Compound 12

Compound 13

Compound 14

Compound 15

Compound 16

Compound 17

Compound 18

Compound 19

Compound 20

Compound 21

Compound 22

Compound 23

Compound 24

Compound 25

Compound 26

Compound 27

Compound 28

Compound 29

Compound 30

Compound 31

Compound 32

Compound 33

Compound 34

Compound 35

Compound 36

Compound 37

Compound 38

Compound 39

Compound 40

Compound 41

Compound 42

Compound 43

Compound 44

Compound 45

Compound 46

Compound 47

Compound 48

Compound 49

Compound 50

Compound 51

Compound 52

Compound 53

Compound 54

Compound 55

Compound 56

Compound 57

Compound 58

Compound 59

Compound 60

Compound 61

Compound 62

Compound 63

Compound 64

Compound 65

Compound 66

Compound 67

Compound 68

Compound 69

Compound 70

Compound 71

Compound 72

Compound 73

Compound 74

Compound 75

Compound 76

Compound 77

Compound 78

Compound 79

Compound 80

Compound 81

Compound 82

Compound 83

Compound 84

Compound 85

Compound 86

Compound 87

Compound 88

Compound 89

Compound 90

Compound 91

Compound 92

Compound 93

Compound 94

Compound 95

Compound 96

Compound 97

Compound 98

Compound 99

Compound 100

Compound 101

Compound 102

Compound 103

Compound 104

Compound 105

Compound 106

Compound 107

Compound 108

Compound 109

Compound 110

Compound 111

Compound 112

Compound 113

Compound 114

Compound 115

Compound 116

Compound 117

Compound 118

Compound 119

Compound 120

Compound 121

Compound 122

Compound 123

Compound 124

Compound 125

Compound 126

Compound 127

Compound 128

Compound 129

Compound 130

Compound 131

Compound 132

Compound 133

Compound 134

Compound 135

Compound 136

Compound 137

Compound 138

Compound 139

Compound 140

Compound 141

Compound 142

Compound 143

Compound 144

Compound 145

Compound 146

Compound 147

Compound 148

Compound 149

Compound 150

Compound 151

Compound 152

Compound 153

Compound 154

Compound 155

Compound 156

Compound 157

Compound 158

Compound 159

Compound 160

Compound 161

Compound 162

Compound 163

Compound 164

Compound 165

Compound 166

Compound 167

Compound 168

Compound 169

Compound 170

Compound 171

Compound 172

Compound 173

Compound 174

Compound 175

Compound 176

Compound 177

Compound 178

Compound 179

Compound 180

Compound 181

Compound 182

Compound 183

Compound 184

Compound 185

Compound 186

Compound 187

Compound 188

Compound 189

Compound 190

Compound 191

Compound 192

Compound 193

Compound 194

Compound 195

Compound 196

Compound 197

Compound 198

Compound 199

Compound 200

Compound 201

Compound 202

Compound 203

Compound 204

Compound 205

Compound 206

Compound 207

Compound 208

Compound 209

Compound 210

Compound 211

Compound 212

Compound 213

Compound 214

Compound 215

Compound 216

Compound 217

Compound 218

Compound 219

Compound 220

Compound 221

Compound 222

Compound 223

Compound 224

Compound 225

Compound 226

Compound 227

Compound 228

Compound 229

Compound 230

Compound 231

Compound 232

Compound 233

Compound 234

Compound 235

Compound 236

Compound 237

Compound 238

Compound 239

Compound 240

Compound 241

Compound 242

Compound 243

Compound 244

Compound 245

Compound 246

Compound 247

Compound 248

Compound 249

Compound 250

Compound 251

Compound 252

Compound 253

Compound 255

Compound 256

Compound 257

Compound 258

Compound 259

Compound 260

Compound 261

Compound 262

Compound 263

Compound 264

Compound 265

Compound 266

Compound 267

Compound 268

Compound 269

Compound 270

Compound 271

Compound 272

Compound 273

Compound 274

Compound 275

Compound 276

Compound 277

Compound 278

Compound 279

Compound 280

Compound 281

Compound 282

Compound 283

Compound 284

Compound 285

Compound 286

Compound 287

Compound 288

Compound 289

Compound 290

Compound 291

Compound 292

Compound 293

Compound 294

Compound 295

Compound 296

Compound 297

Compound 298

Compound 299

Compound 300

Compound 301

Compound 302

Compound 303

Compound 304

Compound 305

Compound 306

Compound 307

Compound 308

Compound 309

Compound 310

Compound 311

Compound 312

Compound 313

Compound 314

Compound 315

Compound 316

Compound 317

Compound 318

Compound 319

Compound 320

Compound 321

Compound 322

Compound 323

Compound 324

Compound 325

Compound 326

Compound 327

Compound 328

Compound 329

Compound 330

Compound 331

Compound 332

Compound 333

Compound 334

Compound 335

Compound 336

Compound 337

Compound 338

Compound 339

Compound 340

Compound 341

Compound 342

Compound 343

Compound 344

Compound 345

Compound 346

Compound 347

Compound 348

Compound 349

Compound 350

Compound 351

Compound 352

Compound 353

Compound 354

Compound 355

Compound 356

Compound 357

Compound 358

Compound 359

Compound 360

Compound 361

Compound 362

Compound 363

Compound 364

Compound 366

Compound 367

Compound 368

Compound 369

Compound 370

Compound 371

Compound 372

Compound 373

Compound 374

Compound 375

Compound 376

Compound 377

Compound 378

Compound 379

Compound 380

Compound 381

Compound 382

Compound 383

Compound 384

Compound 385

Compound 386

Compound 387

Compound 388

Compound 389

Compound 390

Compound 391

Compound 392

Compound 393

Compound 394

Compound 395

Compound 396

Compound 397

Compound 398

Compound 399

Compound 400

Compound 401

Compound 402

Compound 403

Compound 404

Compound 405

Compound 406

Compound 407

Compound 408

Compound 409

Compound 410

Compound 411

Compound 412

Compound 413

Compound 414

Compound 415

Compound 416

Compound 417

Compound 418

Compound 419

Compound 420

Compound 421

Compound 422

Compound 423

Compound 424

Compound 425

Compound 426

Compound 427

Compound 428

Compound 429

Compound 430

Compound 431

Compound 432

Compound 433

Compound 434

Compound 435

Compound 436

Compound 437

Compound 438

Compound 439

Compound 440

Compound 441

Compound 442

Compound 443

Compound 444

Compound 445

Compound 446

Compound 447

Compound 448

Compound 449

Compound 450

Compound 451

Compound 452

Compound 453

Compound 454

Compound 455

Compound 456

Compound 457

Compound 458

Compound 459

Compound 460

Compound 461

Compound 462

Compound 463

Compound 464

Compound 465

Compound 466

Compound 467

Compound 468

Compound 469

Compound 470

Compound 471

Compound 472

Compound 473

Compound 474

Compound 475

Compound 476

Compound 477

Compound 478

Compound 479

Compound 480

Compound 481

Compound 482

Compound 483

Compound 484

Compound 485

Compound 486

Compound 487

Compound 488

Compound 489

Compound 490

Compound 491

Compound 492

Compound 493

Compound 494

Compound 495

Compound 496

Compound 497

Compound 498

Compound 499

Compound 500

Compound 501

Compound 502

Compound 503

Compound 504

Compound 505

Compound 506

Compound 507

Compound 508

Compound 509

Compound 510

Compound 511

Compound 512

Compound 513

Compound 514

Compound 515

Compound 516

Compound 517

Compound 518

Compound 519

Compound 521

Compound 522

Compound 523

Compound 524

Compound 525

Compound 526

Compound 527

Compound 528

Compound 529

Compound 530

Compound 531

Compound 532

Compound 533

Compound 534

Compound 535

Compound 536

Compound 537

Compound 538

Compound 539

Compound 540

Compound 541

Compound 542

Compound 543

Compound 544

Compound 545

Compound 546

Compound 547

Compound 548

Compound 549

Compound 550

Compound 551

Compound 552

Compound 553

Compound 554

Compound 555

Compound 556

Compound 557

Compound 558

Compound 559

Compound 560

Compound 561

Compound 562

Compound 563

Compound 564

Compound 565

Compound 566

Compound 567

Compound 568

Compound 569

Compound 570

Compound 571

Compound 572

Compound 573

Compound 574

Compound 575

Compound 576

Compound 577

Compound 578

Compound 579

Compound 580

Compound 581

Compound 582

Compound 583

Compound 584

Compound 585

Compound 586

Compound 587

Compound 588

Compound 589

Compound 590

Compound 591

Compound 592

Compound 593

Compound 594

Compound 595

Compound 596

Compound 597

Compound 598

Compound 599

Compound 600

Compound 601

Compound 602

Compound 603

Compound 604

Compound 605

Compound 606

Compound 607

Compound 608

Compound 609

Compound 610

Compound 611

Compound 612

Compound 613

Compound 614

Compound 615

Compound 616

Compound 617

Compound 618

Compound 619

Compound 620

Compound 621

Compound 622

Compound 623

Compound 624

Compound 625

Compound 626

Compound 627

Compound 628

Compound 629

Compound 630

Compound 631

Compound 632

Compound 633

Compound 634

Compound 635

Compound 636

Compound 637

Compound 638

Compound 639

Compound 640

Compound 641

Compound 642

Compound 643

Compound 644

Compound 645

Compound 646

Compound 647

Compound 648

Compound 649

Compound 650

Compound 651

Compound 652

Compound 653

Compound 654

Compound 655

Compound 656

Compound 657

Compound 658

Compound 659

Compound 660

Compound 661

Compound 662

Compound 663

Compound 664

Compound 665

Compound 666

Compound 667

Compound 668

Compound 669

Compound 670

Compound 671

Compound 672

Compound 673

Compound 674

Compound 675

Compound 676

Compound 677

Compound 678

Compound 679

Compound 680

Compound 681

Compound 682

Compound 683

Compound 684

Compound 685

Compound 686

Compound 687

Compound 688

Compound 689

Compound 690

Compound 691

Compound 692

Compound 693

Compound 694

Compound 695

Compound 696

Compound 697

Compound 698

Compound 699

Compound 700

Compound 701

Compound 702

Compound 703

Compound 704

Compound 705

Compound 706

Compound 707

Compound 708

Compound 709

Compound 710

Compound 711

Compound 712

Compound 713

Compound 714

Compound 715

Compound 716

Compound 717

Compound 718

Compound 719

Compound 720

Compound 721

Compound 722

Compound 723

Compound 724

Compound 725

Compound 726

Compound 727

Compound 728

Compound 729

Compound 730

Compound 731

Compound 732

Compound 733

Compound 734

Compound 735

Compound 736

Compound 737

Compound 738

Compound 739

Compound 740

Compound 741

Compound 742

Compound 743

Compound 744

Compound 745

Compound 746

Compound 747

Compound 748

Compound 749

Compound 750

Compound 751

Compound 752

Compound 753

Compound 754

Compound 755

Compound 756

Compound 757

Compound 758

Compound 759

Compound 760

Compound 761

Compound 762

Compound 763

Compound 764

Compound 765

Compound 766

Compound 767

Compound 768

Compound 769

Compound 770

Compound 771

Compound 772

Compound 773

Compound 774

Compound 775

Compound 776

Compound 777

Compound 778

Compound 779

Compound 780

Compound 781

Compound 782

Compound 783

Compound 784

Compound 785

Compound 786

Compound 787

Compound 788

Compound 789

Compound 790

Compound 791

Compound 792

Compound 793

Compound 794

Compound 795

Compound 796

Compound 797

Compound 798

Compound 799

Compound 800

Compound 801

Compound 802

Compound 803

Compound 804

Compound 805

Compound 806

Compound 807

Compound 808

Compound 809

Compound 810

Compound 811

Compound 812

Compound 813

Compound 814

Compound 815

Compound 816

Compound 817

Compound 818

Compound 819

Compound 820

Compound 821

Compound 822

Compound 823

Compound 824

Compound 825

Compound 826

Compound 827

Compound 828

Compound 829

Compound 830

Compound 831

Compound 832

Compound 833

Compound 834

Compound 835

Compound 836

Compound 837

Compound 838

Compound 839

Compound 840

Compound 841

Compound 842

Compound 843

Compound 844

Compound 845

Compound 846

Compound 847

Compound 848

Compound 849

Compound 850

Compound 851

Compound 852

Compound 853

Compound 854

Compound 855

Compound 856

Compound 857

Compound 858

Compound 859

Compound 860

Compound 861

Compound 862

Compound 863

Compound 864

Compound 865

Compound 866

Compound 867

Compound 868

Compound 869

Compound 870

Compound 871

Compound 872

Compound 873

Compound 874

Compound 875

Compound 876

Compound 877

Compound 878

Compound 879

Compound 880

Compound 881

Compound 882

Compound 883

Compound 884

Compound 885

Compound 886

Compound 887

Compound 888

Compound 889

Compound 890

Compound 891

Compound 892

Compound 893

Compound 894

Compound 895

Compound 896

Compound 897

Compound 898

Compound 899

Compound 900

Compound 901

Compound 902

Compound 903

Compound 904

Compound 905

Compound 906

Compound 907

Compound 908

Compound 909

Compound 910

Compound 911

Compound 912

Compound 913

Compound 914

Compound 915

Compound 916

Compound 917

Compound 918

Compound 919

Compound 920

Compound 921

Compound 922

Compound 923

Compound 924

Compound 925

Compound 926

Compound 927

Compound 928

Compound 929

Compound 930

Compound 931

Compound 932

Compound 933

Compound 934

Compound 935

Compound 936

Compound 937

Compound 938

Compound 939

Compound 940

Compound 941

Compound 942

Compound 943

Compound 944

Compound 945

Compound 946

Compound 947

Compound 948

Compound 949

Compound 950

Compound 951

Compound 952

Compound 953

Compound 954

Compound 955

Compound 956

Compound 957

Compound 958

Compound 959

Compound 960

Compound 961

Compound 962

Compound 963

Compound 964

Compound 965

Compound 966

Compound 967

Compound 968

Compound 969

Compound 970

Compound 971

Compound 972

Compound 973

Compound 974

Compound 975

Compound 976

Compound 977

Compound 978

Compound 979

Compound 980

Compound 981

Compound 982

Compound 983

Compound 984

Compound 985

Compound 986

Compound 987

Compound 988

Compound 989

Compound 990

Compound 991

Compound 992

Compound 993

Compound 995

Compound 996

Compound 997

Compound 998

Compound 999

Compound 1000

Compound 1001

Compound 1002

Compound 1003

Compound 1004

Compound 1005

Compound 1006

Compound 1007

Compound 1008

Compound 1009

Compound 1010

Compound 1011

Compound 1012

Compound 1013

Compound 1014

Compound 1015

Compound 1016

Compound 1017

Compound 1018

Compound 1019

Compound 1020

Compound 1021

Compound 1022

Compound 1023

Compound 1024

Compound 1025

Compound 1026

Compound 1027

Compound 1028

Compound 1029

Compound 1030

Compound 1031

Compound 1032

Compound 1033

Compound 1034

Compound 1035

Compound 1036

Compound 1037

Compound 1038

Compound 1039

Compound 1040

Compound 1041

Compound 1042

Compound 1043

Compound 1044

Compound 1045

Compound 1046

Compound 1047

Compound 1048

Compound 1049

Compound 1050

Compound 1051

Compound 1052

Compound 1053

Compound 1054

Compound 1055

Compound 1056

Compound 1057

Compound 1058

Compound 1059

Compound 1060

Compound 1061

Compound 1062

Compound 1063

Compound 1064

Compound 1065

Compound 1066

Compound 1067

Compound 1068

Compound 1069

Compound 1070

Compound 1071

Compound 1072

Compound 1073

Compound 1074

Compound 1075

Compound 1076

Compound 1077

Pharmacological Test Example 1: Experiment of Sodium-Dependent Phosphate Uptake of Xenopus Oocytes which Expressed NaPi-2b

Degenerate primers were prepared from sequences of mouse NaPi-2b disclosed in Hilfiker H. et al., Pro Natl Acad Sci USA, 95 (24): 14564-14569, 1988 and sequences of human and rat NaPi-2a disclosed in Magagnin S. et al., Proc Natl Aca Sci USA, 90 (13): 5979-5983, 1993. RNA was extracted from the rat small intestine using ISOGEN; manufactured by NIPPON GENE CO., LTD (Japan). 400 bp gene fragments were obtained by PCR using, as a template, a cDNA library prepared with a cDNA synthesis kit (manufactured by STRATAGENE (US)). Thereafter, the above rat small intestine cDNA library was screened using the gene fragment as a probe, and the whole gene sequence of rat NaPi-2b was cloned. cRNA was synthesized from the cloned rat NaPi-2b cDNA with a cRNA synthesis kit (manufactured by Ambion (US)). The synthesized cRNA was injected into Xenopus oocytes (obtained from COPACETIC (Japan)) with a liquid microinjector (manufactured by Drummond (US)) and was cultured for 2 days to express rat NaPi-2b. Thereafter, for a group of derivatives, phosphate uptake inhibitory activity were measured using the Xenopus oocytes with ³²P radioactive phosphorus (manufactured by Daiichi Kagaku Inc. (Japan)). As a result, it was found that these compounds had inhibitory activity with IC₅₀ values as shown in Table 4. IC₅₀ values were determined by determining an inhibition curve by an approximation formula using the least square from inhibitory activity values obtained from five concentration levels of the compound and determining the concentration of the compound which exhibits 50% of the maximum inhibitory activity. The inhibitory activity for 300 μM and 100 μM was determined from the same inhibition curve and expressed in percentage inhibition (%) in Table 5.

TABLE 4 Compound No. IC50 (μM) Compound 1 9.11 Compound 3 7.15 Compound 4 79.93 Compound 5 3.31 Compound 6 5.38 Compound 7 7.15 Compound 8 1.72 Compound 9 4.26 Compound 10 26.12 Compound 11 8.21 Compound 12 4.51 Compound 13 9.22 Compound 14 12.10 Compound 15 1.41 Compound 16 2.30 Compound 17 3.59 Compound 18 4.03 Compound 19 8.16 Compound 20 2.83 Compound 21 21.53 Compound 22 26.67 Compound 23 9.88 Compound 24 20.92 Compound 25 23.91 Compound 26 25.37 Compound 27 3.63 Compound 28 5.12 Compound 29 0.55 Compound 30 7.86 Compound 31 0.58 Compound 32 1.95 Compound 33 15.02 Compound 34 1.50 Compound 35 3.23 Compound 36 4.04 Compound 37 13.47 Compound 38 5.64 Compound 39 9.24 Compound 40 2.03 Compound 41 2.43 Compound 42 8.21 Compound 43 20.66 Compound 44 4.71 Compound 45 26.14 Compound 46 7.41 Compound 47 4.38 Compound 48 2.07 Compound 49 3.37 Compound 50 19.48 Compound 51 4.60 Compound 52 10.39 Compound 53 4.05 Compound 54 6.45 Compound 55 0.86 Compound 56 0.89 Compound 57 1.02 Compound 58 7.67 Compound 59 1.22 Compound 60 1.58 Compound 61 0.31 Compound 62 0.90 Compound 63 5.97 Compound 64 3.77 Compound 65 1.29 Compound 66 0.89 Compound 67 0.65 Compound 68 0.36 Compound 69 3.93 Compound 70 9.51 Compound 71 12.33 Compound 72 10.41 Compound 73 1.75 Compound 74 2.15 Compound 75 12.77 Compound 76 13.17 Compound 77 3.01 Compound 78 7.17 Compound 79 2.87 Compound 80 10.87 Compound 81 5.65 Compound 82 6.03 Compound 83 2.98 Compound 84 8.42 Compound 85 2.00 Compound 86 11.4 Compound 87 0.29 Compound 88 0.22 Compound 89 1.11 Compound 90 3.42 Compound 91 0.22 Compound 92 0.26 Compound 93 10.98 Compound 94 5.63 Compound 95 1.27 Compound 96 5.94 Compound 97 0.51 Compound 98 0.62 Compound 99 3.03 Compound 100 0.64 Compound 101 0.75 Compound 102 5.58 Compound 103 5.73 Compound 104 11.34 Compound 105 7.29 Compound 106 5.11 Compound 107 1.08 Compound 108 3.83 Compound 109 6.18 Compound 110 7.70 Compound 111 9.12 Compound 112 41.98 Compound 113 17.91 Compound 114 2.55 Compound 115 5.48 Compound 116 7.01 Compound 117 0.58 Compound 118 6.07 Compound 119 0.74 Compound 120 2.55 Compound 121 4.06 Compound 122 <3.00 Compound 123 3.77 Compound 124 3.15 Compound 125 136.43 Compound 126 6.43 Compound 127 11.59 Compound 128 11.61 Compound 129 13.70 Compound 130 11.42 Compound 132 0.75 Compound 133 0.88 Compound 134 7.82 Compound 135 3.74 Compound 136 4.52 Compound 137 3.00 Compound 138 4.47 Compound 139 55.50 Compound 140 74.24 Compound 141 5.78 Compound 142 9.20 Compound 143 5.88 Compound 144 5.02 Compound 145 3.82 Compound 146 1.99 Compound 147 7.68 Compound 148 15.63 Compound 149 5.51 Compound 150 1.09 Compound 151 3.07 Compound 152 1.48 Compound 153 3.50 Compound 154 2.37 Compound 155 0.32 Compound 156 0.46 Compound 157 7.19 Compound 158 3.28 Compound 159 4.35 Compound 160 0.93 Compound 161 0.96 Compound 162 3.11 Compound 163 1.60 Compound 164 4.76 Compound 165 2.43 Compound 166 27.85 Compound 167 30.20 Compound 168 4.84 Compound 169 4.24 Compound 170 5.34 Compound 171 5.12 Compound 172 2.74 Compound 173 7.40 Compound 174 12.54 Compound 175 3.57 Compound 176 4.10 Compound 177 26.01 Compound 178 7.54 Compound 179 18.69 Compound 180 <3.00 Compound 181 3.16 Compound 182 10.24 Compound 183 <3.00 Compound 184 4.01 Compound 185 2.02 Compound 186 10.1 Compound 187 7.87 Compound 188 19.43 Compound 189 1.47 Compound 190 20.32 Compound 191 12.12 Compound 192 23.09 Compound 193 4.21 Compound 194 7.36 Compound 195 0.98 Compound 196 0.61 Compound 197 4.87 Compound 198 2.71 Compound 199 1.82 Compound 200 0.39 Compound 201 11.10 Compound 202 3.14 Compound 203 <3.00 Compound 204 <3.00 Compound 205 <3.00 Compound 206 <3.00 Compound 207 <1.00 Compound 208 <0.30 Compound 209 <1.00 Compound 210 34.96 Compound 211 69.07 Compound 212 71.27 Compound 213 16.64 Compound 214 3.95 Compound 215 <3.00 Compound 216 21.82 Compound 217 11.21 Compound 218 4.05 Compound 219 9.07 Compound 220 9.42 Compound 221 9.51 Compound 222 8.86 Compound 223 11.30 Compound 224 19.99 Compound 225 60.98 Compound 226 1.69 Compound 227 7.40 Compound 228 22.48 Compound 229 6.32 Compound 252 1.49 Compound 253 3.47 Compound 255 3.54 Compound 256 <10.00 Compound 257 <3.00 Compound 258 <3.00 Compound 259 <3.00 Compound 260 <3.00 Compound 261 <3.00 Compound 262 1.10 Compound 263 <1.00 Compound 264 <1.00 Compound 265 <1.00 Compound 266 <1.00 Compound 267 0.43 Compound 268 1.02 Compound 269 2.19 Compound 270 5.04 Compound 271 0.21 Compound 272 0.47 Compound 273 0.15 Compound 274 1.04 Compound 275 1.73 Compound 276 6.20 Compound 277 1.60 Compound 278 0.16 Compound 279 2.31 Compound 280 0.78 Compound 281 4.60 Compound 282 6.71 Compound 283 22.44 Compound 284 26.94 Compound 285 0.90 Compound 286 0.57 Compound 287 0.11 Compound 288 1.31 Compound 289 2.89 Compound 290 3.25 Compound 291 1.16 Compound 292 3.50 Compound 293 5.59 Compound 294 7.80 Compound 295 7.58 Compound 296 1.45 Compound 297 0.96 Compound 298 9.22 Compound 299 3.91 Compound 300 1.92 Compound 301 15.17 Compound 302 1.12 Compound 303 1.13 Compound 304 1.23 Compound 305 2.47 Compound 306 2.13 Compound 307 41.17 Compound 308 2.76 Compound 309 15.12 Compound 310 7.82 Compound 311 7.78 Compound 312 3.31 Compound 313 1.24 Compound 314 3.39 Compound 315 9.02 Compound 316 4.71 Compound 317 5.02 Compound 318 2.49 Compound 319 9.76 Compound 320 4.09 Compound 321 2.66 Compound 322 5.93 Compound 323 4.69 Compound 324 4.43 Compound 325 2.56 Compound 326 2.10 Compound 327 5.12 Compound 328 1.15 Compound 329 5.63 Compound 330 10.69 Compound 331 15.76 Compound 332 2.87 Compound 333 17.18 Compound 334 7.69 Compound 335 5.86 Compound 336 16.63 Compound 337 1.39 Compound 338 18.97 Compound 339 12.77 Compound 340 8.41 Compound 341 <3.00 Compound 342 32.60 Compound 343 124.10 Compound 344 30.99 Compound 345 129.95 Compound 346 4.46 Compound 347 4.91 Compound 348 16.59 Compound 349 8.78 Compound 350 25.32 Compound 351 8.96 Compound 352 13.00 Compound 353 8.85 Compound 354 1.54 Compound 356 0.17 Compound 358 54.07 Compound 359 7.10 Compound 360 0.63 Compound 361 <1.00 Compound 362 <1.00 Compound 363 <1.00 Compound 364 <1.00 Compound 367 6.88 Compound 368 1.37 Compound 369 1.45 Compound 370 1.86 Compound 371 2.54 Compound 372 0.80 Compound 373 1.68 Compound 374 9.25 Compound 375 24.71 Compound 376 21.00 Compound 377 9.65 Compound 378 4.35 Compound 379 0.97 Compound 380 0.35 Compound 381 1.00 Compound 382 1.04 Compound 383 1.98 Compound 384 0.25 Compound 385 0.31 Compound 386 <3.00 Compound 387 6.45 Compound 388 19.67 Compound 389 1.09 Compound 390 0.45 Compound 391 1.02 Compound 392 1.42 Compound 393 0.52 Compound 394 0.95 Compound 395 8.55 Compound 396 8.19 Compound 397 9.25 Compound 398 <0.30 Compound 399 3.67 Compound 400 <0.30 Compound 401 6.13 Compound 402 14.12 Compound 403 26.73 Compound 404 2.18 Compound 405 1.90 Compound 406 0.88 Compound 407 0.57 Compound 408 0.69 Compound 409 2.52 Compound 410 4.05 Compound 411 10.08 Compound 412 7.96 Compound 413 <3.00 Compound 414 <3.00 Compound 415 <3.00 Compound 416 3.25 Compound 417 <3.00 Compound 418 9.38 Compound 419 9.20 Compound 420 27.14 Compound 421 29.56 Compound 422 1.15 Compound 423 <3.00 Compound 424 1.79 Compound 425 <3.00 Compound 426 1.89 Compound 427 <3.00 Compound 428 1.82 Compound 429 5.88 Compound 430 4.53 Compound 431 5.57 Compound 432 22.22 Compound 433 14.34 Compound 434 7.78 Compound 435 7.65 Compound 436 8.36 Compound 437 <3.00 Compound 438 26.27 Compound 439 28.74 Compound 440 32.35 Compound 441 40.14 Compound 442 3.15 Compound 443 11.05 Compound 444 <3.00 Compound 445 10.33 Compound 446 1.54 Compound 447 2.16 Compound 448 9.41 Compound 449 21.73 Compound 450 16.94 Compound 451 37.84 Compound 452 <3.00 Compound 453 <3.00 Compound 454 <3.00 Compound 455 <3.00 Compound 456 <3.00 Compound 457 <3.00 Compound 458 <3.00 Compound 459 <3.00 Compound 460 <3.00 Compound 461 3.59 Compound 462 <3.00 Compound 463 4.44 Compound 464 5.00 Compound 465 7.43 Compound 466 <3.00 Compound 467 7.94 Compound 468 22.45 Compound 469 33.16 Compound 470 23.54 Compound 472 <3.00 Compound 473 <3.00 Compound 474 <3.00 Compound 475 <3.00 Compound 476 <3.00 Compound 477 <3.00 Compound 478 <3.00 Compound 479 <3.00 Compound 480 <3.00 Compound 481 12.10 Compound 482 <3.00 Compound 483 <3.00 Compound 484 <3.00 Compound 485 <3.00 Compound 486 <3.00 Compound 487 <3.00 Compound 488 <3.00 Compound 489 <3.00 Compound 490 <3.00 Compound 491 <3.00 Compound 492 <3.00 Compound 493 <3.00 Compound 494 2.07 Compound 495 0.35 Compound 496 0.64 Compound 497 0.51 Compound 498 0.60 Compound 499 0.98 Compound 500 0.35 Compound 501 23.13 Compound 502 15.68 Compound 503 10.35 Compound 504 18.93 Compound 505 1.21 Compound 506 19.5 Compound 507 1.86 Compound 508 0.48 Compound 509 13.59 Compound 510 1.48 Compound 511 2.16 Compound 512 28.30 Compound 513 15.96 Compound 514 2.15 Compound 515 1.90 Compound 516 2.13 Compound 517 1.71 Compound 518 1.52 Compound 519 1.72 Compound 521 1.24 Compound 522 1.09 Compound 551 0.47 Compound 552 2.63 Compound 553 2.80 Compound 554 1.46 Compound 555 <3.00 Compound 556 <3.00 Compound 557 <0.30 Compound 558 1.07 Compound 559 1.26 Compound 560 1.09 Compound 561 0.31 Compound 562 <1.00 Compound 563 <1.00 Compound 564 11.57 Compound 565 12.98 Compound 566 14.58 Compound 567 <1.00 Compound 568 4.32 Compound 569 <3.00 Compound 570 6.04 Compound 571 5.27 Compound 572 4.12 Compound 573 1.75 Compound 574 6.93 Compound 575 <3.00 Compound 576 <3.00 Compound 577 <3.00 Compound 578 <3.00 Compound 579 <3.00 Compound 580 <3.00 Compound 581 <3.00 Compound 582 <3.00 Compound 583 <3.00 Compound 584 <3.00 Compound 585 <3.00 Compound 586 <3.00 Compound 587 <3.00 Compound 588 9.33 Compound 589 <3.00 Compound 590 6.18 Compound 591 1.01 Compound 592 11.94 Compound 593 <3.00 Compound 594 3.60 Compound 595 3.87 Compound 596 5.47 Compound 597 1.47 Compound 598 53.04 Compound 599 <3.00 Compound 600 3.84 Compound 601 <3.00 Compound 602 3.98 Compound 603 <3.00 Compound 604 9.23 Compound 605 0.95 Compound 606 1.01 Compound 607 0.43 Compound 608 <0.30 Compound 609 <0.30 Compound 610 1.82 Compound 611 2.16 Compound 612 2.34 Compound 613 1.41 Compound 614 3.29 Compound 615 2.08 Compound 616 13.86 Compound 617 3.68 Compound 618 4.25 Compound 619 <3.00 Compound 620 3.58 Compound 621 <3.00 Compound 622 <3.00 Compound 623 <3.00 Compound 624 <3.00 Compound 625 <3.00 Compound 626 <3.00 Compound 627 <1.00 Compound 628 1.29 Compound 629 3.01 Compound 630 <1.00 Compound 631 <1.00 Compound 632 <1.00 Compound 633 1.19 Compound 634 1.74 Compound 635 1.56 Compound 636 3.89 Compound 637 <1.00 Compound 638 3.15 Compound 639 1.84 Compound 640 1.61 Compound 641 2.92 Compound 642 2.14 Compound 643 3.68 Compound 644 5.91 Compound 645 <3.00 Compound 646 1.77 Compound 647 5.62 Compound 648 2.04 Compound 649 2.69 Compound 650 0.95 Compound 651 262.90 Compound 652 0.72 Compound 653 1.10 Compound 654 2.03 Compound 655 1.58 Compound 656 2.98 Compound 657 2.63 Compound 658 <3.00 Compound 659 12.45 Compound 660 18.70 Compound 661 <10.00 Compound 662 3.20 Compound 663 136.67 Compound 664 15.08 Compound 666 31.23 Compound 667 30.49 Compound 668 9.13 Compound 669 15.29 Compound 671 <3.00 Compound 672 31.18 Compound 673 10.13 Compound 675 <3.00 Compound 676 <3.00 Compound 677 <3.00 Compound 678 <3.00 Compound 679 <3.00 Compound 680 4.04 Compound 681 25.90 Compound 682 12.50 Compound 683 <3.00 Compound 684 54.25 Compound 685 36.43 Compound 686 <3.00 Compound 687 <3.00 Compound 688 <3.00 Compound 689 <3.00 Compound 690 87.97 Compound 691 97.03 Compound 692 99.40 Compound 693 70.18 Compound 694 38.77 Compound 695 6.76 Compound 696 4.47 Compound 697 <3.00 Compound 698 <3.00 Compound 713 15.49 Compound 714 3.52 Compound 718 6.91 Compound 719 9.59 Compound 720 3.51 Compound 721 22.34 Compound 722 12.84 Compound 723 18.03 Compound 724 17.08 Compound 725 69.40 Compound 726 <3.00 Compound 728 20.33 Compound 729 27.33 Compound 730 15.66 Compound 731 19.18 Compound 732 29.35 Compound 733 <10.00 Compound 735 18.34 Compound 737 4.24 Compound 738 7.55 Compound 743 14.40 Compound 745 6.12 Compound 746 16.77 Compound 747 11.93 Compound 749 9.05 Compound 750 <3.00 Compound 751 13.11 Compound 752 <3.00 Compound 753 12.36 Compound 754 <3.00 Compound 756 10.33 Compound 757 18.84 Compound 763 11.18 Compound 764 5.92 Compound 765 6.88 Compound 768 10.62 Compound 769 4.44 Compound 770 16.49 Compound 786 1.33 Compound 787 1.69 Compound 788 2.04 Compound 789 1.16 Compound 790 4.32 Compound 791 5.50 Compound 792 1.26 Compound 793 1.41 Compound 794 0.97 Compound 795 1.92 Compound 796 0.35 Compound 797 3.39 Compound 798 3.62 Compound 799 3.72 Compound 800 9.24 Compound 801 4.70 Compound 802 1.20 Compound 803 4.92 Compound 804 1.23 Compound 805 4.76 Compound 806 3.90 Compound 807 <1.00 Compound 808 1.97 Compound 809 5.22 Compound 810 6.68 Compound 811 9.11 Compound 812 5.58 Compound 813 6.25 Compound 814 <3.00 Compound 815 16.74 Compound 816 14.77 Compound 817 36.14 Compound 818 7.38 Compound 819 5.95 Compound 820 17.86 Compound 821 17.86 Compound 822 5.90 Compound 823 6.93 Compound 824 3.22 Compound 825 4.52 Compound 826 4.44 Compound 827 3.50 Compound 828 9.33 Compound 829 3.91 Compound 830 4.81 Compound 831 3.88 Compound 832 4.97 Compound 833 7.89 Compound 834 19.02 Compound 835 6.46 Compound 836 0.77 Compound 837 12.91 Compound 838 <3.00 Compound 839 5.04 Compound 840 6.95 Compound 841 <3.00 Compound 842 3.22 Compound 843 4.19 Compound 844 <3.00 Compound 845 <3.00 Compound 846 <3.00 Compound 847 <3.00 Compound 848 2.20 Compound 849 <3.00 Compound 850 3.10 Compound 851 1.36 Compound 852 <1.00 Compound 853 2.14 Compound 854 1.33 Compound 855 1.75 Compound 856 1.77 Compound 857 1.18 Compound 858 0.46 Compound 859 0.39 Compound 860 0.65 Compound 861 0.52 Compound 862 0.35 Compound 863 1.22 Compound 864 0.74 Compound 865 1.49 Compound 866 1.92 Compound 867 2.24 Compound 868 <0.30 Compound 869 6.68 Compound 870 0.53 Compound 871 1.00 Compound 872 <3.00 Compound 873 0.66 Compound 874 <0.30 Compound 875 5.20 Compound 876 <3.00 Compound 877 <0.30 Compound 878 <0.30 Compound 879 3.72 Compound 880 0.08 Compound 881 0.18 Compound 882 0.33 Compound 883 0.04 Compound 884 0.95 Compound 885 1.24 Compound 886 0.81 Compound 887 1.75 Compound 888 2.55 Compound 889 0.33 Compound 890 3.91 Compound 891 1.47 Compound 892 14.84 Compound 893 <0.30 Compound 894 0.50 Compound 895 <0.30 Compound 896 <0.30 Compound 897 <0.30 Compound 898 <0.30 Compound 899 <1.00 Compound 900 <1.00 Compound 901 <1.00 Compound 902 <1.00 Compound 903 <1.00 Compound 904 1.71 Compound 905 1.18 Compound 906 1.83 Compound 907 6.75 Compound 908 13.16 Compound 909 1.02 Compound 910 7.81 Compound 911 <1.00 Compound 912 1.04 Compound 913 1.65 Compound 914 1.75 Compound 915 8.15 Compound 916 5.22 Compound 917 1.25 Compound 918 1.55 Compound 919 0.31 Compound 920 <1.00 Compound 921 1.22 Compound 922 2.89 Compound 923 18.79 Compound 924 40.16 Compound 925 25.50 Compound 926 <1.00 Compound 927 <1.00 Compound 928 <1.00 Compound 929 <1.00 Compound 935 0.17 Compound 936 5.59 Compound 937 137.00 Compound 938 1.41 Compound 939 <3.00 Compound 940 30.63 Compound 941 8.72 Compound 942 0.20 Compound 943 10.58 Compound 944 12.04 Compound 945 19.38 Compound 947 30.19 Compound 948 11.62 Compound 950 9.08 Compound 952 19.24 Compound 954 60.51 Compound 956 29.85 Compound 958 <1.00 Compound 959 <1.00 Compound 960 1.12 Compound 961 <1.00 Compound 962 <1.00 Compound 963 <1.00 Compound 965 27.22 Compound 966 16.04 Compound 967 6.57 Compound 969 <3.00 Compound 970 <3.00 Compound 971 <3.00 Compound 972 <3.00 Compound 973 <3.00 Compound 974 12.56 Compound 975 17.36 Compound 976 10.73 Compound 977 10.15 Compound 980 13.80 Compound 981 12.17 Compound 982 8.05 Compound 983 8.31 Compound 984 22.12 Compound 985 <3.00 Compound 986 28.95 Compound 987 <3.00 Compound 988 3.88 Compound 989 <3.00 Compound 990 <3.00 Compound 996 2.66 Compound 997 7.88 Compound 998 16.57 Compound 999 58.16 Compound 1001 <3.00 Compound 1002 2.58 Compound 1003 9.12 Compound 1006 6.31 Compound 1007 0.40 Compound 1008 0.30 Compound 1009 0.10 Compound 1010 0.24 Compound 1011 1.28 Compound 1012 1.89 Compound 1013 8.89 Compound 1015 11.07 Compound 1016 9.23 Compound 1017 0.87 Compound 1018 0.92 Compound 1019 0.41 Compound 1020 0.39 Compound 1021 5.57 Compound 1022 3.23 Compound 1023 0.99 Compound 1024 3.94 Compound 1025 5.71 Compound 1026 3.86 Compound 1027 1.20 Compound 1028 29.07 Compound 1029 34.73 Compound 1030 14.16 Compound 1033 18.66 Compound 1034 17.21 Compound 1035 3.70 Compound 1036 1.50 Compound 1037 38.51 Compound 1038 3.35 Compound 1039 2.76 Compound 1040 52.16 Compound 1041 10.25 Compound 1042 14.74 Compound 1043 8.26 Compound 1044 2.13 Compound 1045 13.11 Compound 1046 <1.00 Compound 1047 <1.00 Compound 1048 <1.00 Compound 1049 <1.00 Compound 1050 1.42 Compound 1051 1.16 Compound 1052 1.33 Compound 1053 <1.00 Compound 1054 <1.00 Compound 1055 1.96 Compound 1056 1.88 Compound 1057 1.26 Compound 1058 1.07 Compound 1059 0.43 Compound 1060 0.44 Compound 1061 1.99 Compound 1062 6.76 Compound 1064 <1.00 Compound 1065 1.21 Compound 1066 2.69 Compound 1067 2.79 Compound 1069 <1.00 Compound 1070 <1.00 Compound 1071 <1.00 Compound 1072 3.88 Compound 1073 20.36 Compound 1074 1.54 Compound 1075 1.34 Compound 1076 2.57

TABLE 5 Compound No. Inhibition (%) (300 μM) Compound 2 77.30 Compound 131 32.40 Compound 230 50.42 Compound 231 32.76 Compound 232 44.92 Compound 233 33.62 Compound 234 37.88 Compound 235 47.92 Compound 236 49.42 Compound 237 33.12 Compound 238 30.58 Compound 239 59.08 Compound 240 37.92 Compound 241 46.94 Compound 242 37.61 Compound 243 50.17 Compound 244 30.72 Compound 245 31.68 Compound 246 32.62 Compound 247 34.81 Compound 248 30.30 Compound 249 41.59 Compound 250 37.86 Compound 251 31.22 Compound 357 65.82 Compound 366 69.87 Compound 471 50.99 Compound 523 50.09 Compound 524 42.75 Compound 525 38.89 Compound 526 40.24 Compound 527 40.94 Compound 528 58.38 Compound 529 80.96 Compound 530 38.16 Compound 531 35.68 Compound 532 76.00 Compound 533 36.87 Compound 534 43.82 Compound 535 52.98 Compound 536 88.25 Compound 537 82.05 Compound 538 30.31 Compound 539 88.39 Compound 540 38.41 Compound 541 32.16 Compound 542 41.11 Compound 543 30.2 Compound 544 60.05 Compound 545 88.81 Compound 546 85.19 Compound 547 66.61 Compound 548 85.72 Compound 549 85.10 Compound 550 78.88 Compound 665 82.34 Compound 670 70.17 Compound 674 85.12 Compound 699 58.35 Compound 700 40.28 Compound 701 53.98 Compound 702 49.17 Compound 703 57.92 Compound 704 46.62 Compound 705 44.68 Compound 706 47.79 Compound 707 41.22 Compound 708 42.04 Compound 709 59.36 Compound 710 83.13 Compound 711 81.04 Compound 712 48.73 Compound 715 84.11 Compound 716 85.77 Compound 717 53.54 Compound 727 67.74 Compound 734 64.91 Compound 736 61.49 Compound 739 58.89 Compound 740 58.55 Compound 741 50.93 Compound 742 77.57 Compound 744 83.71 Compound 748 56.45 Compound 755 67.27 Compound 758 58.21 Compound 759 63.85 Compound 760 73.34 Compound 761 46.24 Compound 762 52.08 Compound 766 81.89 Compound 767 81.83 Compound 771 85.12 Compound 772 67.72 Compound 773 53.91 Compound 774 58.85 Compound 775 44.62 Compound 776 49.19 Compound 777 34.17 Compound 778 39.12 Compound 779 51.64 Compound 780 47.74 Compound 781 51.18 Compound 782 86.76 Compound 783 88.84 Compound 784 88.49 Compound 785 39.53 Compound 930 40.20 Compound 931 31.22 Compound 932 36.09 Compound 933 37.62 Compound 934 39.27 Compound 946 45.00 Compound 949 72.60 Compound 951 68.51 Compound 953 67.80 Compound 955 57.67 Compound 957 54.91 Compound 964 67.50 Compound 968 52.70 Compound 978 74.08 Compound 979 73.73 Compound 991 30.11 Compound 992 31.92 Compound 993 39.71 Compound 995 42.10 Compound 1000 32.14 Compound 1004 34.20 Compound 1005 59.07 Compound 1014 55.20 Compound 1031 58.77 Compound 1032 39.98 Compound 1077 40.18 Inhibition (%) (100 μM) Compound 1063 63.94 Compound 1068 74.42

Pharmacological Test Example 2: Experiment of Sodium-Dependent Phosphate Uptake of Rabbit Jejunal Brush Border Membrane Vesicles

Jejunal epithelium was obtained from New Zealand white male rabbits (7 weeks old, obtained from KITAYAMA LABES Co., Ltd. (Japan)), and brush border membrane vesicles were isolated by the calcium precipitation method described in Kanako Katai et al., J. Biochem. 121, 50-55, 1997, and Peerce, B. E. et al., Biochemistry 26, 4272-4279, 1987. Thereafter, for compound 29 and compound 68, the phosphate uptake inhibitory activity was measured using the same samples with ³²P radioactive phosphorus (manufactured by Daiichi Kagaku Inc. (Japan)) by the rapid filtration method described in Kanako Katai et al., J. Biochem. 121, 50-55, 1997. As a result, these compounds had concentration-dependent inhibitory activity (FIG. 1). Further, in the same experiment, nonspective inhibitory activity against glucose absorption was determined using 14C-glucose (manufactured by Moravek Biochemical Inc. (US)). As a result, these compounds did not have the inhibitory activity (FIG. 2). In both the experiments, a group with the addition of potassium chloride was used as a negative control for nonspecific uptake. All the test results given below were expressed in terms of average value±standard error. Student's t-test was used for a significant test of the control group and the test compound group.

Pharmacological Test Example 3: Experiment of Sodium-Dependent Phosphate Uptake of Xenopus Oocytes which Expressed NaPi-2a

cDNA of human NaPi-2a described in Magagnin S. et al., Proc Natl Aca Sci USA, 90 (13): 5979-5983, 1993 was cloned by PCR. In the same manner as in Pharmacological Test Example 1, NaPi-2a was expressed in Xenopus oocytes, and the phosphate uptake inhibitory activity was measured with ³²P radioactive phosphorus. As a result, compound 1 had concentration-dependent inhibitory activity against NaPi-2a (FIG. 3). Compound 29 had inhibitory activity against not only NaPi-2b but also NaPi-2a (FIG. 4). In the test, a group with the addition of choline chloride (Choline Cl) was used as a negative control for nonspecific uptake, and PFA (phosphonoformic acid) was used as a positive control for phosphate transport inhibition.

Further, the compounds according to the present invention had inhibitory activity with IC₅₀ values shown in Table 6. IC₅₀ values were determined by determining an inhibition curve by an approximation formula using the least square from inhibitory activity values obtained from five concentration levels of the compound and determining the concentration of the compound which exhibits 50% of the maximum inhibitory activity.

TABLE 6 IC50 (μM) Compound 260 <3.00 Compound 262 4.42 Compound 264 4.36 Compound 591 4.04 Compound 592 9.51 Compound 627 3.53 Compound 628 3.59 Compound 629 12.94 Compound 630 3.50 Compound 631 2.43 Compound 632 28.66 Compound 633 13.46 Compound 634 16.87 Compound 635 1.34 Compound 636 5.30 Compound 637 0.95 Compound 638 4.22 Compound 639 11.15 Compound 640 15.59 Compound 641 7.53 Compound 642 13.30 Compound 786 <3.00 Compound 787 <3.00 Compound 788 6.64 Compound 789 9.28 Compound 791 6.70 Compound 793 8.46 Compound 794 9.57 Compound 795 8.52 Compound 800 10.05 Compound 801 3.72 Compound 802 5.96 Compound 806 12.14 Compound 807 9.07 Compound 810 23.81 Compound 811 37.22 Compound 813 35.59 Compound 814 18.34 Compound 818 31.43 Compound 822 18.01 Compound 824 8.19 Compound 827 24.37 Compound 828 10.02 Compound 829 <3.00 Compound 830 10.73 Compound 831 28.83 Compound 832 6.40 Compound 833 38.11 Compound 834 52.10 Compound 835 10.98 Compound 836 10.18 Compound 838 10.17 Compound 839 23.15 Compound 840 34.06 Compound 841 19.85 Compound 845 <3.00 Compound 846 <3.00 Compound 858 <1.00 Compound 859 1.60 Compound 860 <1.00 Compound 861 <1.00 Compound 862 1.65 Compound 863 6.90 Compound 864 1.94 Compound 865 4.34 Compound 878 7.22 Compound 880 1.30 Compound 881 2.67 Compound 882 4.45 Compound 883 1.98 Compound 884 35.90 Compound 886 2.93 Compound 887 15.06 Compound 889 1.41 Compound 890 1.33 Compound 891 13.86 Compound 893 5.11 Compound 894 3.61 Compound 895 5.52 Compound 896 7.40 Compound 899 <1.00 Compound 900 2.53 Compound 901 <1.00 Compound 902 <1.00 Compound 903 <1.00 Compound 904 1.69 Compound 914 3.13 Compound 935 9.68 Compound 936 30.05 Compound 985 <3.00 Compound 987 16.31 Compound 989 7.84 Compound 990 7.14 Compound 1007 1.00 Compound 1008 2.30 Compound 1009 1.41 Compound 1020 2.25 Compound 1027 1.58 Pharmacological Test Example 4: Inhibitory Activity Against ³²P Absorption from Intestinal Tract

SD rats (6 to 7 weeks old, obtained from Charles River Japan, Inc. (Japan)) were raised with low-phosphorus diet (phosphorus content 0.1%, manufactured by Oriental Yeast Co., Ltd. (Japan)) for 3 to 4 days and then fasted for about 24 hr for experiment. ³²P was diluted with purified water or liquid feed (CLEA JAPAN INC. (Japan)) to 0.7 to 3.5 MBq/ml and was forcibly orally administered at a dose of 5 ml/kg (administered into the gaster through an oral probe). The compounds or media were forcibly orally administered at a dose of 5 ml/kg (divided dose of twice), 30 min before the administration of ³²P and simultaneously with the administration of ³²P. Blood was collected from caudal artery 30 min, 45 min, or 60 min after ³²P administration, and blood ³²P radioactivity was measured with a liquid scintillation counter. Inhibition of an increase in blood radioactivity was used as a measure of inhibition of phosphate absorption from the intestinal tract.

The results are expressed in terms of the percentage inhibition determined by the following equation.

(Blood radioactivity for group with the administration of medium−Blood radioactivity for group with the administration of compound)/(Blood radioactivity for group with the administration of medium)×100

t-Test was used for a significant test of the average value difference of blood radioactivity.

The results are shown in Table 7. As is apparent from the table, the compounds significantly inhibited phosphate absorption from the intestinal tract.

TABLE 7 Inhibitory activity against ³²P absorption from intestinal tract Blood radioactivity Compound Dose, mg/kg inhibition, % 91 320 28.3 92 160 25.5 88 400 29.1 163 360 57.8 130 270 22.8 157 320 20.7 164 400 55.0 165 400 27.6 252 400 29.2 253 400 39.0 254 400 68.4 315 100 42.4 372 100 63.7 285 80 60.3 For all the compounds, a significant difference was observed as compared with the group with the administration of medium at p<0.05. 

1-49. (canceled)
 50. A compound represented by represented by formula (I-1), or a pharmaceutically acceptable salt thereof:

wherein A represents formula (IIa):

wherein R¹, R², R³, and R⁴, which may be the same or different, represent (a) a halogen atom; (b) hydroxyl; (c) C₁₋₆ alkyl; (d) C₁₋₆ alkoxy; (e) aryl; (f) aryloxy; (g) arylthio; (h) alkylthio; (i) nitro; (j) amino; (k) mono- or di-arylamino; (l) mono- or di-C₁₋₆ alkylamino; (m) C₂₋₆ alkenyl; (n) C₂₋₆ alkenyloxy; (o) C₂₋₆ alkenylthio; (p) mono- or di-C₂₋₆ alkenylamino; (q) carboxyl; (r) C₁₋₆ alkyl- or aryl-oxycarbonyl; or (s) a hydrogen atom, (c) the C₁₋₆ alkyl group, (d) the C₁₋₆ alkoxy group, (e) the aryl group, (f) the aryloxy group, (g) the arylthio group, (h) the alkylthio group, (m) the C₂₋₆ alkenyl group, (n) the C₂₋₆ alkenyloxy group, and (o) the C₂₋₆ alkenylthio group are optionally substituted by (1) hydroxyl, (2) thiol, (3) amino, (4) C₁₋₆ alkoxy, (5) C₁₋₆ alkylthio, (6) C₁₋₆ alkylsulfonyl, (7) mono- or di-C₁₋₆ alkylamino in which the di-C₁₋₆ alkylamino group may form cyclic amino optionally containing 1 to 3 heteroatoms, (8) aryloxy, (9) arylthio, (10) arylsulfonyl, (11) aryl, (12) a heterocyclic group, (13) a halogen atom, or (14) arylamino in which the amino group is optionally substituted by C₁₋₆ alkyl, and the aryl group is optionally substituted by halogen, C₁₋₆ alkyl, C₁₋₆ alkoxy, or C₁₋₆ alkylamino, (15) C₁₋₆ alkoxy-(CH₂CH₂O)_(m) wherein m is an integer of 1 to 6, (16) carboxyl, (17) an oxygen atom (═O), or (18) C₃₋₇ cycloalkyl, the aryl moiety in (k) the mono- or di-arylamino group is optionally substituted by (1) hydroxyl, (2) thiol, (3) amino, (4) C₁₋₆ alkoxy, (5) C₁₋₆ alkylthio, (6) C₁₋₆ alkylsulfonyl, (7) mono- or di-C₁₋₆ alkylamino in which the di-C₁₋₆ alkylamino group may form cyclic amino optionally containing 1 to 3 heteroatoms, (8) aryloxy, (9) arylthio, (10) arylsulfonyl, (11) aryl, (12) a heterocyclic group, (13) a halogen atom, (14) arylamino in which the amino group is optionally substituted by C₁₋₆ alkyl, and the aryl group is optionally substituted by a halogen atom, C₁₋₆ alkyl, C₁₋₆ alkoxy, or C₁₋₆ alkylamino, (15) C₁₋₆ alkoxy-(CH₂CH₂O)_(m) wherein m is an integer of 1 to 6, (16) carboxyl, (17) an oxygen atom (═O), or (18) C₃₋₇ cycloalkyl, and, in the case of the mono-arylamino group, the amino group is optionally substituted by C₁₋₆ alkyl optionally substituted by hydroxyl or a halogen atom, in (1) the mono- or di-C₁₋₆ alkylamino, the di-C₁₋₆ alkyl group may form cyclic amino optionally containing 1 to 3 heteroatoms, and one or two alkyl groups on the amino group and the cyclic amino moiety are optionally substituted by a halogen atom; C₁₋₆ alkyl optionally substituted by hydroxyl, a halogen atom, or aryl optionally substituted by a halogen atom, C₁₋₆ alkyl, or C₁₋₆ alkyloxy, a heterocyclic group optionally substituted by a halogen atom, C₁₋₆ alkyl, or C₁₋₆ alkyloxy, and, when one or two alkyl groups on the amino group and the cyclic amino moiety are substituted by two C₁₋₆ alkyl groups, they together may form C₃₋₇ cycloalkyl; C₁₋₆ alkoxy; C₁₋₆ alkylthio; mono- or di-C₁₋₆ alkylamino in which the di-C₁₋₆ alkylamino group may form cyclic amino optionally containing 1 to 3 heteroatoms, and one or two C₁₋₆ alkyl groups on the amino group and the cyclic amino moiety are optionally substituted by hydroxyl or a halogen atom; arylamino in which the amino group is optionally substituted by C₁₋₆ alkyl; mono- or di-C₁₋₆ alkylcarbamoylmethyl in which the di-C₁₋₆ alkylamino group may form cyclic amino optionally containing 1 to 3 heteroatoms, and one or two alkyl groups on the amino group and the cyclic amino moiety are optionally substituted by hydroxyl; aryloxy; arylthio; an oxygen atom (═O); hydroxyl; carboxyl; C₁₋₆ alkoxy- or aryloxy-carbonyl; C₁₋₆ alkylcarbonyl; aryl optionally substituted by a halogen atom or hydroxyl; or a heterocyclic group, in (p) the mono- or di-C₁₋₆ alkenylamino group, the amino group of the monoalkenylamino group is optionally substituted by C₁₋₆ alkyl optionally substituted by hydroxyl or a halogen atom, and the di-C₂₋₆ alkenyl together may form unsaturated cyclic amino optionally containing 1 to 3 heteroatoms, and one or two alkenyl groups on the amino group or the unsaturated cyclic amino moiety is optionally substituted by a halogen atom; C₁₋₆ alkyl optionally substituted by hydroxyl, a halogen atom, aryl optionally substituted by a halogen atom, C₁₋₆ alkyl, or C₁₋₆ alkyloxy, a heterocyclic group optionally substituted by a halogen atom, C₁₋₆ alkyl, or C₁₋₆ alkyloxy, and, when one or two alkyl groups on the amino group and the cyclic amino moiety are substituted by two C₁₋₆ alkyl groups, they together may form C₃₋₇ cycloalkyl; C₁₋₆ alkoxy; C₁₋₆ alkylthio; mono- or di-C₁₋₆ alkylamino in which the di-C₁₋₆ alkylamino group may form cyclic amino optionally containing 1 to 3 heteroatoms, and one or two C₁₋₆ alkyl groups on the amino group and the cyclic amino moiety are optionally substituted by hydroxyl or a halogen atom; arylamino in which the amino group is optionally substituted by C₁₋₆ alkyl; mono- or di-C₁₋₆ alkylcarbamoylmethyl in which the di-C₁₋₆ alkylamino group may form cyclic amino optionally containing 1 to 3 heteroatoms, and one or two alkyl groups on the amino group and the cyclic amino moiety are optionally substituted by hydroxyl; aryloxy; arylthio; an oxygen atom (═O); hydroxyl; carboxyl; C₁₋₆ alkoxy- or aryloxy-carbonyl; C₁₋₆ alkylcarbonyl; aryl optionally substituted by a halogen atom or hydroxyl; or a heterocyclic group, when two of R¹, R², R³, and R⁴ are (c) C₁₋₆ alkyl groups or (m) C₂₋₆ alkenyl groups, the alkyl or the alkenyl groups together with the carbon atoms to which they are respectively attached may form an unsaturated five- to seven-membered carbocyclic ring, and * represents a bond to —C(═O)—NH(Z)— ---- represents a double bond, R⁵ represents optionally substituted C₅₋₇ cycloalkyl, optionally substituted aryl, or optionally substituted saturated or unsaturated five- or six-membered heterocyclic group, wherein R⁵ is optionally substituted by (I) a halogen atom; (II) C₁₋₆ alkyl optionally containing a substituent selected from the group consisting of (1) hydroxyl, (2) thiol, (3) amino, (4) C₁₋₆ alkoxy, (5) C₁₋₆ alkylthio, (6) C₁₋₆ alkylsulfinyl, (7) C₁₋₆ alkylsulfonyl, (8) mono- or di C₁₋₆ alkylamino, (8′) amino substituted by a heterocyclic group optionally substituted by C₁₋₆ alkyl, (9) C₁₋₆ alkylcarbonyloxy, (10) C₁₋₆ alkylcarbonylthio, (11) C₁₋₆ alkylcarbonylamino, (12) aryloxy, (13) arylthio, (14) arylsulfinyl, (15) arylsulfonyl, (16) arylamino, (17) C₁₋₆ alkyl- or aryl-sulfonylamino, (18) C₁₋₆ alkyl- or aryl-ureido, (19) C₁₋₆ alkoxy- or aryloxy-carbonylamino, (20) C₁₋₅ alkylamino- or arylaminocarbonyloxy, (21) carboxyl, (22) nitro, (23) a heterocyclic group, (23′) Het-S(═O)j wherein Het represents a heterocyclic group, j is 0, 1, or 2, and the Het is optionally substituted by alkyl optionally substituted by mono- or di-C₁₋₆ alkylamino in which the di-C₁₋₆ alkylamino group may form cyclic amino optionally containing 1 to 3 heteroatoms and one or two alkyl groups on the amino group and the cyclic amino moiety are optionally substituted by hydroxyl, (24) cyano, and (25) a halogen atom, wherein the alkyl moiety in (4) the C₁₋₆ alkoxy group, (5) the C₁₋₆ alkylthio group, (6) the C₁₋₆ alkylsulfinyl group, and (7) the C₁₋₆ alkylsulfonyl group is optionally substituted by a halogen atom; C₁₋₆ alkyl; C₁₋₆ alkoxy; C₁₋₆ alkylthio; mono- or di-C₁₋₆ alkylamino in which the di-C₁₋₆ alkylamino group may form cyclic amino optionally containing 1 to 3 heteroatoms; aryloxy; arylthio; hydroxyl; carboxyl; —S(═O)₂(—OH); C₁₋₆ alkoxy- or aryloxy-carbonyl; C₁₋₆ alkylcarbonyl; aryl; or a heterocyclic group optionally substituted by alkyl optionally substituted by mono- or di-C₁₋₆ alkylamino in which the di-C₁₋₆ alkylamino group may form cyclic amino optionally containing 1 to 3 heteroatoms, and one or two alkyl groups on the amino group and the cyclic amino moiety are optionally substituted by hydroxy, and in (8) the mono- or di-C₁₋₆ alkylamino group, the di-C₁₋₆ alkylamino group may form cyclic amino optionally containing 1 to 3 heteroatoms, and one or two alkyl groups on the amino group and the cyclic amino moiety are optionally substituted by a halogen atom; C₁₋₆ alkyl optionally substituted by hydroxyl, a halogen atom, aryl optionally substituted by a halogen atom, C₁₋₆ alkyl, or C₁₋₆ alkyloxy, or a heterocyclic group optionally substituted by a halogen atom, C₁₋₆ alkyl, or C₁₋₆ alkyloxy, and, when one or two alkyl groups on the amino group and the cyclic amino moiety are substituted by two C₁₋₆ alkyl groups, they together may form C₃₋₇ cycloalkyl; C₁₋₆ alkoxy; C₁₋₆ alkylthio; mono- or di-C₁₋₆ alkylamino in which the di-C₁₋₆ alkylamino may form cyclic amino optionally containing 1 to 3 heteroatoms, and one or two alkyl groups on the amino group and the cyclic amino moiety are optionally substituted by hydroxyl; arylamino in which the amino group is optionally substituted by C₁₋₆ alkyl; mono- or di-C₁₋₆ alkylcarbamoylmethyl in which the di-C₁₋₆ alkylamino group may form cyclic amino optionally containing 1 to 3 heteroatoms, and one or two alkyl groups on the amino group and the cyclic amino moiety are optionally substituted by hydroxyl; aryloxy; arylthio; an oxygen atom (═O); hydroxyl; carboxyl; C₁₋₆ alkoxy- or aryloxy-carbonyl; C₁₋₆ alkylcarbonyl; aryl optionally substituted by a halogen atom or hydroxyl; or a heterocyclic group, and, when one carbon atom in the cyclic amino moiety is substituted by two C₁₋₆ alkoxy groups which may be the same or different, the two alkoxy groups together may form group —O—(CH2)_(p)—O— wherein p is an integer of 2 to 4, and the cyclic amino group may condense with a monocyclic or bicyclic aromatic carbocyclic ring or a monocyclic or bicyclic aromatic heterocyclic ring to represent a bicyclic or tricyclic heterocyclic group; (III) C₁₋₆ alkoxy optionally substituted by a halogen atom; (IV) C₁₋₆ alkylthio optionally substituted by a halogen atom; (V) C₃₋₇ cycloalkyl; (VI) aryl; (VII) aryloxy; (VIII) C₁₋₆ alkylcarbonylamino; (VIX) C₁₋₆ alkylcarbonyloxy; (X) hydroxyl; (XI) nitro; (XII) cyano; (XIII) amino; (XIV) mono or di-C₁₋₆ alkylamino in which the di-C₁₋₆ alkylamino group may form cyclic amino optionally containing 1 to 3 heteroatoms; (XV) arylamino; (XVI) C₁₋₆ alkyl- or aryl-sulfonylamino; (XVII) C₁₋₆ alkyl- or aryl-ureido; (XVIII) C₁₋₆ alkoxy- or aryloxy-carbonylamino; (XIX) C₁₋₆ alkylamino- or arylamino-carbonyloxy; (XX) C₁₋₆ alkoxy- or aryloxy-carbonyl; (XXI) acyl; (XXII) carboxyl; (XXIII) carbamoyl; (XXIV) mono- or di-alkylcarbamoyl; (XXV) a heterocyclic group; (XXVI) alkyl- or aryl-sulfonyl; (XXVII) C₂₋₆ alkenyloxy group; or (XXVIII) C₂₋₆ alkenyloxy, Z represents group (A) or group (B):

wherein R⁶ represents a hydrogen atom or C₁₋₆ alkyl, R⁷ represents optionally substituted aryl, optionally substituted aryl C₁₋₆ alkyl, optionally substituted aryl C₂₋₆ alkenyl, or optionally substituted saturated or unsaturated five- or six-membered heterocyclic group, wherein R⁷ is optionally substituted by. (I) a halogen atom; (II) C₁₋₆ alkyl optionally having a substituent selected from a group consisting of (1) hydroxyl, (2) thiol, (3) amino, (4) C₁₋₆ alkoxy, (5) C₁₋₆ alkylthio optionally substituted by hydroxyl, (6) C₁₋₆ alkylsulfinyl, (7) C₁₋₆ alkylsulfonyl, (8) mono- or di-C₁₋₆ alkylamino in which the di-C₁₋₆ alkylamino group may form cyclic amino optionally containing 1 to 3 heteroatoms, (9) C₁₋₆ alkylcarbonyloxy, (10) C₁₋₆ alkylcarbonylthio, (11) C₁₋₆ alkylcarbonylamino, (12) aryloxy, (13) arylthio, (14) arylsulfinyl, (15) arylsulfonyl, (16) arylamino, (17) C₁₋₈ alkyl- or aryl-sulfonylamino, (18) C₁₋₆ alkyl- or aryl-ureido, (19) C₁₋₆ alkoxy- or aryloxy-carbonylamino, (20) C₁₋₆ alkylamino- or arylamino-carbonyloxy, (21) carboxyl, (22) nitro, (23) a heterocyclic group, (23′) Het-S— wherein Het represents a heterocyclic group, (24) cyano, (25) a halogen atom, and (26) C₁₋₆ alkyl- or aryl-oxycarbonyl; (III) C₁₋₆ alkoxy optionally having a substituent selected from the group consisting of (1) hydroxyl, (2) thiol, (3) amino, (4) C₁₋₆ alkoxy, (5) C₁₋₆ alkylthio optionally substituted by hydroxyl, (6) C₁₋₆ alkylsulfinyl, (7) C₁₋₆ alkylsulfonyl, (8) mono- or di-C₁₋₆ alkylamino in which the di-C₁₋₆ alkylamino group may form cyclic amino optionally containing 1 to 3 heteroatoms, (9) C₁₋₆ alkylcarbonyloxy, (10) C₁₋₆ alkylcarbonylthio, (11) C₁₋₆ alkylcarbonylamino, (12) aryloxy, (13) arylthio, (14) arylsulfinyl, (15) arylsulfonyl, (16) arylamino, (17) C₁₋₆ alkyl- or aryl-sulfonylamino, (18) C₁₋₈ alkyl- or aryl-ureido, (19) C₁₋₆ alkoxy- or aryloxy-carbonylamino, (20) C₁₋₆ alkylamino- or arylamino-carbonyloxy, (21) carboxyl, (22) nitro, (23) a heterocyclic group, (23′) Het-S— wherein the Het represents a heterocyclic group, (24) cyano, (25) a halogen atom, and (26) C₁₋₆ alkyl- or aryl-oxycarbonyl; (IV) C₁₋₆ alkylthio optionally substituted by a halogen atom; (V) C₃₋₇ cycloalkyl; (VI) aryl; (VII) aryloxy; (VIII) C₁₋₆ alkylcarbonylamino; (VIX) C₁₋₆ alkylcarbonyloxy; (X) hydroxyl; (XI) nitro; (XII) cyano; (XIII) amino; (XIV) mono- or di-C₁₋₆ alkylamino in which the di-C₁₋₆ alkylamino may form cyclic amino optionally containing 1 to 3 heteroatoms; (XV) arylamino; (XVI) C₁₋₆ alkyl- or aryl-sulfonylamino; (XVII) C₁₋₆ alkyl- or aryl-ureido; (XVIII) C₁₋₆ alkoxy- or aryloxy-carbonylamino; (XIX) C₁₋₆ alkylamino- or arylamino-carbonyloxy; (XX) C₁₋₆ alkoxy- or aryloxy-carbonyl; (XXI) aryl; (XXII)carboxyl; (XXIII) carbamoyl; (XXIV) mono- or di-alkylcarbamoyl; (XXV) a heterocyclic groups; (XXVI) alkyl- or aryl-sulfonyl; (XXVII) C₂₋₆ alkenyloxy; or (XXVIII) C₂₋₆ alkynyloxy, R¹⁷ represents a hydrogen atom. 51-55. (canceled)
 56. The compound according to claim 50, wherein R⁵ represents formula (IIIa), formula (IIIb), or formula (IIIc)

wherein D, E, J, L, and M, which may be the same or different, represent a carbon or nitrogen atom, G represents an oxygen or sulfur atom, R⁸, R⁹, R¹⁰, R¹¹, and R¹², which may be the same or different, represent (I) a halogen atom; (II) C₁₋₆ alkyl optionally containing a substituent selected from the group consisting of (1) hydroxyl, (2) thiol, (3) amino, (4) C₁₋₆ alkoxy, (5) C₁₋₆ alkylthio, (6) C₁₋₆ alkylsulfinyl, (7) C₁₋₆ alkylsulfonyl, (8) mono- or di-C₁₋₆ alkylamino, (8′) amino substituted by a heterocyclic group optionally substituted by C₁₋₆ alkyl, (9) C₁₋₆ alkylcarbonyloxy, (10) C₁₋₆ alkylcarbonylthio, (11) C₁₋₆ alkylcarbonylamino, (12) aryloxy, (13) arylthio, (14) arylsulfinyl, (15) arylsulfonyl, (16) arylamino, (17) C₁₋₆ alkyl- or aryl-sulfonylamino, (18) C₁₋₆ alkyl- or aryl-ureido, (19) C₁₋₆ alkoxy- or aryloxy-carbonylamino, (20) C₁₋₆ alkylamino- or arylamino-carbonyloxy, (21) carboxyl, (22) nitro, (23) a heterocyclic group, (23′) Het-S(═O)j- wherein the Het represents a heterocyclic group, j is 0, 1, or 2, and Het is optionally substituted by alkyl optionally substituted by mono- or di-C₁₋₆ alkylamino in which the di-C₁₋₆ alkylamino group may form cyclic amino optionally containing 1 to 3 heteroatoms and one or two alkyl groups on the amino group and the cyclic amino moiety are optionally substituted by hydroxyl, (24) cyano, and (25) a halogen atom, wherein the alkyl moiety in (4) the C₁₋₆ alkoxy group, (5) the C₁₋₆ alkylthio group, (6) the C₁₋₆ alkylsulfinyl group, and (7) the C₁₋₆ alkylsulfonyl group is optionally substituted by a hydrogen atom; a halogen atom; C₁₋₆ alkyl; C₁₋₆ alkoxy; C₁₋₆ alkylthio; mono- or di-C₁₋₆ alkylamino in which the di-C₁₋₆ alkylamino group may form cyclic amino optionally containing 1 to 3 heteroatoms; aryloxy; arylthio; hydroxyl; carboxyl; —S(═O)₂(—OH); C₁₋₆ alkoxy- or aryloxy-carbonyl; C₁₋₆ alkylcarbonyl; aryl; or a heterocyclic group optionally substituted by alkyl optionally substituted by mono- or di-C₁₋₆ alkylamino in which the di-C₁₋₆ alkylamino group may form cyclic amino optionally containing 1 to 3 heteroatoms, and one or two alkyl groups on the amino group and the cyclic amino moiety are optionally substituted by hydroxy, and in (8) the mono- or di-C₁₋₆ alkylamino group, the di-C₁₋₆ alkylamino group may form cyclic amino optionally containing 1 to 3 heteroatoms, and one or two alkyl groups on the amino group and the cyclic amino moiety are optionally substituted by a halogen atom; C₁₋₆ alkyl optionally substituted by hydroxyl, a halogen atom, aryl optionally substituted by a halogen atom, C₁₋₆ alkyl, or C₁₋₆ alkyloxy, or a heterocyclic group optionally substituted by a halogen atom, C₁₋₆ alkyl, or C₁₋₆ alkyloxy, and, when one or two alkyl groups on the amino group and the cyclic amino moiety are substituted by two C₁₋₆ alkyl groups, they together may form C₃₋₇ cycloalkyl; C₁₋₆ alkoxy; C₁₋₆ alkylthio; mono- or di-C₁₋₆ alkylamino in which the di-C₁₋₆ alkylamino may form cyclic amino optionally containing 1 to 3 heteroatoms, and one or two alkyl groups on the amino group and the cyclic amino moiety are optionally substituted by hydroxyl; arylamino in which the amino group is optionally substituted by C₁₋₆ alkyl; mono- or di-C₁₋₆ alkylcarbamoylmethyl in which the di-C₁₋₆ alkylamino group may form cyclic amino optionally containing 1 to 3 heteroatoms, and one or two alkyl groups on the amino group and the cyclic amino moiety are optionally substituted by hydroxyl; aryloxy; arylthio; an oxygen atom (═O); hydroxyl; carboxyl; C₁₋₆ alkoxy- or aryloxy-carbonyl; C₁₋₆ alkylcarbonyl; aryl optionally substituted by a halogen atom or hydroxyl; or a heterocyclic group, and, when one carbon atom in the cyclic amino moiety is substituted by two C₁₋₆ alkoxy groups which may be the same or different, the two alkoxy groups together may form group —O—(CH₂)_(p)—O— wherein p is an integer of 2 to 4, and the cyclic amino group may condense with a monocyclic or bicyclic aromatic carbocyclic ring or a monocyclic or bicyclic aromatic heterocyclic ring to represent a bicyclic or tricyclic heterocyclic group; (III) C₁₋₆ alkoxy optionally substituted by a halogen atom; (IV) C₁₋₆ alkylthio optionally substituted by a halogen atom; (V) C₃₋₇ cycloalkyl; (VI) aryl; (VII) aryloxy; (VIII) C₁₋₆ alkylcarbonylamino; (VIX) C₁₋₆ alkylcarbonyloxy; (X) hydroxyl; (XI) nitro; (XII) cyano; (XIII) amino; (XIV) mono- or di-C₁₋₆ alkylamino in which the di-C₁₋₆ alkylamino group may form cyclic amino optionally containing 1 to 3 heteroatoms; (XV) arylamino; (XVI) C₁₋₆ alkyl- or aryl-sulfonylamino; (XVII) C₁₋₆ alkyl- or aryl-ureido; (XVIII) C₁₋₆ alkoxy- or aryloxy-carbonylamino; (XIX) C₁₋₆ alkylamino- or arylamino-carbonyloxy; (XX) C₁₋₆ alkoxy- or aryloxy-carbonyl; (XXI) acyl; (XXII) carboxyl; (XXIII) carbamoyl; (XXIV) mono- or di-alkylcarbamoyl; (XXV) a heterocyclic group; (XXVI) alkyl- or aryl-sulfonyl; (XXVII) C₂₋₆ alkenyloxy; (XXVIII) C₂₋₆ alkynyloxy; or (XXIX) a hydrogen atom, and when D, E, J, L, or M represents a nitrogen atom, R⁸, R⁹, R¹⁰, R¹¹, and R¹² each are absent, or otherwise may combine with a nitrogen atom to form N-oxide (N→O).
 57. The compound according to claim 50, wherein A represents formula (IIa):

wherein (1) R¹, R², R³, and R⁴ represent a hydrogen atom, (2) R¹ and R⁴ represent a hydrogen atom, any one of R² and R³ represents a halogen atom; hydroxyl; optionally substituted C₁₋₆ alkyl; optionally substituted C₁₋₆ alkoxy; optionally substituted mono- or di-arylamino; optionally substituted mono- or di-C₁₋₆ alkylamino in which the dialkylamino together may form optionally substituted cyclic amino optionally containing 1 to 3 heteroatoms; or optionally substituted mono- or di-C₂₋₆ alkenylamino in which the di-C₂₋₆ alkenylamino group together may form optionally substituted unsaturated cyclic amino optionally containing 1 to 3 heteroatoms, and the other represents a hydrogen atom, (3) R¹ and R⁴ represent a hydrogen atom, and R² and R³, which may be the same or different, represent a halogen atom; hydroxyl; optionally substituted C₁₋₆ alkyl; or optionally substituted C₁₋₆ alkoxy, (4) R¹ and R⁴ represent a hydrogen atom, and R² and R³ together with the carbon atoms to which they are respectively attached form an unsaturated five- to seven-membered carbocyclic ring, (5) R¹ and R⁴ represent a hydrogen atom, any one of R² and R³ represents optionally substituted mono- or di-C₁₋₆ alkylamino in which the di-C₁₋₆ alkylamino together may form optionally substituted cyclic amino optionally containing 1 to 3 heteroatoms, and the other represents a hydrogen atom, or (6) R¹ and R⁴ represent a hydrogen atom, any one of R² and R³ represents optionally substituted C₁₋₆ alkoxy, and the other represents a hydrogen atom, and * represents a bond to —C(═O)—NH(—Z) R⁵ represents formula (IIIa)

wherein (i) D, E, J, L, and M represent a carbon atom, any one or two of R⁸, R⁹, R¹⁰, R¹¹, and R¹², which may be the same or different, represent a halogen atom; hydroxymethyl; C₁₋₆ alkyl optionally substituted by a halogen atom; or C₁₋₆ alkoxy optionally substituted by a halogen atom, and the others represent a hydrogen atom, (ii) any one or two of D, E, J, L, and M represent a nitrogen atom, and the others represent a carbon atom, any one or two of R⁸, R⁹, R¹⁰, R¹¹, and R¹² may be the same or different and represent a halogen atom; hydroxymethyl; C₁₋₆ alkyl optionally substituted by a halogen atom, or C₁₋₆ alkoxy optionally substituted by a halogen atom, and the others represent a hydrogen atom, (iii) D, E, J, L, and M represent a carbon atom, R⁸, R⁹, and R¹² represent a hydrogen atom, any one of R¹⁰ and R¹¹ represents a group of formula (IV) —CH₂-Q—X1-R¹³  (IV) wherein Q represents an oxygen atom, a sulfur atom, sulfinyl, or sulfonyl, X1 represents a bond or straight chain or branched chain alkylene having 1 to 5 carbon atoms, R¹³ represents a hydrogen atom, a halogen atom, C₁₋₆ alkyl, C₁₋₆ alkoxy, C₁₋₆ alkylthio, mono- or di-C₁₋₆ alkylamino in which the di-C₁₋₆ alkylamino group may form cyclic amino optionally containing 1 to 3 heteroatoms, aryloxy, arylthio, hydroxyl, carboxyl, —S(═O)₂(—OH), C₁₋₆ alkoxy- or aryloxy-carbonyl, C₁₋₆ alkylcarbonyl, aryl, or a heterocyclic group optionally substituted by alkyl optionally substituted by mono- or di-C₁₋₆ alkylamino in which the di-C₁₋₆ alkylamino group may form cyclic amino optionally containing 1 to 3 heteroatoms, and one or two alkyl groups on the amino group and the cyclic amino moiety are optionally substituted by hydroxyl; or a group of formula (V)

wherein X2 represents a bond or straight chain or branched chain alkylene having 1 to carbon atoms, X3 represents a bond or straight chain or branched chain alkylene having 1 to 5 carbon atoms, R¹⁴ and R¹⁵, which may be the same or different, represent a hydrogen atom; a halogen atom; C₁₋₆ alkyl optionally substituted by hydroxyl, a halogen atom, aryl optionally substituted by a halogen atom, C₁₋₆ alkyl, or C₁₋₆ alkyloxy, a heterocyclic group optionally substituted by a halogen atom, C₁₋₆ alkyl, or C₁₋₆ alkyloxy, and, when one or two alkyl groups on the amino group and the cyclic amino moiety are substituted by two C₁₋₆ alkyl groups, they together may form C₃₋₇ cycloalkyl; C₁₋₆ alkoxy; C₁₋₆ alkylthio; mono- or di-C₁₋₆ alkylamino in which the di-C₁₋₆ alkylamino group may form cyclic amino optionally containing 1 to 3 heteroatoms, and one or two alkyl groups on the amino group and the cyclic amino moiety are optionally substituted by hydroxyl; arylamino in which the amino group is optionally substituted by C₁₋₆ alkyl; mono- or di-C₁₋₆ alkylcarbamoylmethyl in which the di-C₁₋₆ alkylamino may form cyclic amino optionally containing 1 to 3 heteroatoms, and one or two alkyl groups on the amino group and the cyclic amino moiety are optionally substituted by hydroxyl; aryloxy; arylthio; an oxygen atom (═O); hydroxyl; carboxyl; C₁₋₆ alkoxy- or aryloxy-carbonyl; C₁₋₆ alkylcarbonyl; aryl optionally substituted by a halogen atom or hydroxyl; or a heterocyclic group, provided that, when X2 represents a bond, R¹⁴ represents a hydrogen atom, or when X3 represents a bond, R¹⁵ represents a hydrogen atom, or R¹⁴ and R¹⁵ together with a nitrogen atom to which they are respectively attached to may form a heterocyclic group that may contain 1 to 3 heteroatoms in addition to the nitrogen atom, to which R¹⁴ and R¹⁵ are attached, and is optionally substituted by hydroxyl; C₁₋₆ alkyl optionally substituted by hydroxyl, a halogen atom, aryl optionally substituted by a halogen atom, C₁₋₆ alkyl, or C₁₋₆ alkyloxy, or a heterocyclic group optionally substituted by a halogen atom, C₁₋₆ alkyl, or C₁₋₆ alkyloxy, and, when one or two alkyl groups on the amino group and the cyclic amino moiety are substituted by two C₁₋₆ alkyl groups, they together may form C₃₋₇ cycloalkyl; mono- or di-C₁₋₆ alkylamino in which the di-C₁₋₆ alkylamino may form cyclic amino optionally containing 1 to 3 heteroatoms, and one or two alkyl groups on the amino group and the cyclic amino moiety are optionally substituted by hydroxyl; a saturated or unsaturated five- or six-membered heterocyclic group; mono- or di-C₁₋₆ alkylcarbamoylmethyl in which the di-C₁₋₆ alkylamino group may form cyclic amino optionally containing 1 to 3 heteroatoms, and one or two alkyl groups on the amino group and the cyclic amino moiety are optionally substituted by hydroxyl; phenyl; or an oxygen atom (═O), and, when one carbon atom in the cyclic amino moiety is substituted by two C₁₋₆ alkoxy groups which may be the same or different, the two alkoxy groups together may form group —O—(CH₂)_(p)—O— wherein p is an integer of 2 to 4, and the cyclic amino group may condense with a monocyclic or bicyclic aromatic carbocyclic ring or a monocyclic or bicyclic aromatic heterocyclic ring to represent a bicyclic or tricyclic heterocyclic group; and the other represents a hydrogen atom, or (iv) any one or two of D, E, J, L, and M represent a nitrogen atom, and the others represent a carbon atom, R⁸, R⁹, and R¹² represent a hydrogen atom, and one of R¹⁰ and R¹¹ represents a group of formula (IV) —CH₂-Q-X1-R¹³  (IV) wherein Q represents an oxygen atom, a sulfur atom, sulfinyl, or sulfonyl, X1 represents a bond or straight chain or branched chain alkylene having 1 to 5 carbon atoms, R¹³ represents a hydrogen atom, a halogen atom, C₁₋₆ alkyl, C₁₋₆ alkoxy, C₁₋₆ alkylthio, mono- or di-C₁₋₆ alkylamino in which the di-C₁₋₆ alkylamino group may form cyclic amino optionally containing 1 to 3 heteroatoms, aryloxy, arylthio, hydroxyl, carboxyl, —S(═O)₂(—OH), C₁₋₆ alkoxy- or aryloxy-carbonyl, C₁₋₆ alkylcarbonyl, aryl, or a heterocyclic group optionally substituted by alkyl optionally substituted by mono- or di-C₁₋₆ alkylamino in which the di-C₁₋₆ alkylamino group may form cyclic amino optionally containing 1 to 3 heteroatoms, and one or two alkyl groups on the amino group and the cyclic amino moiety are optionally substituted by hydroxyl; or a group of formula (V)

wherein X2 represents a bond or straight chain or branched chain alkylene having 1 to 5 carbon atoms, X3 represents a bond or straight chain or branched chain alkylene having 1 to 5 carbon atoms, R¹⁴ and R¹⁵, which may be the same or different, represent a hydrogen atom; a halogen atom; C₁₋₆ alkyl optionally substituted by hydroxyl, a halogen atom, aryl optionally substituted by a halogen atom, C₁₋₆ alkyl, or C₁₋₆ alkyloxy, a heterocyclic group optionally substituted by a halogen atom, C₁₋₆ alkyl, or C₁₋₆ alkyloxy, and, when one or two alkyl groups on the amino group and the cyclic amino moiety are substituted by two C₁₋₆ alkyl groups, they together may form C₃₋₇ cycloalkyl; C₁₋₆ alkoxy; C₁₋₆ alkylthio; mono- or di-C₁₋₆ alkylamino in which the di-C₁₋₆ alkylamino group may form cyclic amino optionally containing 1 to 3 heteroatoms, and one or two alkyl groups on the amino group and the cyclic amino moiety are optionally substituted by hydroxyl; arylamino in which the amino group is optionally substituted by C₁₋₆ alkyl; mono- or di-C₁₋₆ alkylcarbamoylmethyl in which the di-C₁₋₆ alkylamino may form cyclic amino optionally containing 1 to 3 heteroatoms, and one or two alkyl groups on the amino group and the cyclic amino moiety are optionally substituted by hydroxyl; aryloxy; arylthio; an oxygen atom (═O); hydroxyl; carboxyl; C₁₋₆ alkoxy- or aryloxy-carbonyl; C₁₋₆ alkylcarbonyl; aryl optionally substituted by a halogen atom or hydroxyl; or a heterocyclic group, provided that, when X2 represents a bond, R¹⁴ represents a hydrogen atom, or when X3 represents a bond, R¹⁵ represents a hydrogen atom, or R¹⁴ and R¹⁵ together with a nitrogen atom to which they are respectively attached to may form a heterocyclic group that may contain 1 to 3 heteroatoms in addition to the nitrogen atom, to which R¹⁴ and R¹⁵ are attached, and is optionally substituted by hydroxyl; C₁₋₆ alkyl optionally substituted by hydroxyl, a halogen atom, aryl optionally substituted by a halogen atom, C₁₋₆ alkyl, or C₁₋₆ alkyloxy, or a heterocyclic group optionally substituted by a halogen atom, C₁₋₆ alkyl, or C₁₋₆ alkyloxy, and, when one or two alkyl groups on the amino group and the cyclic amino moiety are substituted by two C₁₋₆ alkyl groups, they together may form C₃₋₇ cycloalkyl; mono- or di-C₁₋₆ alkylamino in which the di-C₁₋₆ alkylamino may form cyclic amino optionally containing 1 to 3 heteroatoms, and one or two alkyl groups on the amino group and the cyclic amino moiety are optionally substituted by hydroxyl; a saturated or unsaturated five- or six-membered heterocyclic group; mono- or di-C₁₋₆ alkylcarbamoylmethyl in which the di-C₁₋₆ alkylamino group may form cyclic amino optionally containing 1 to 3 heteroatoms, and one or two alkyl groups on the amino group and the cyclic amino moiety are optionally substituted by hydroxyl; phenyl; or an oxygen atom (═O), and, when one carbon atom in the cyclic amino moiety is substituted by two C₁₋₆ alkoxy groups which may be the same or different, the two alkoxy groups together may form group —O—(CH₂)_(p)—O— wherein p is an integer of 2 to 4, and the cyclic amino group may condense with a monocyclic or bicyclic aromatic carbocyclic ring or a monocyclic or bicyclic aromatic heterocyclic ring to represent a bicyclic or tricyclic heterocyclic group; and the other represents a hydrogen atom, Z represents group (A), group (B), or group (C):

wherein R⁶ represents a hydrogen atom or C₁₋₆ alkyl, R⁷ represents optionally substituted aryl, optionally substituted aryl C₁₋₆ alkyl, optionally substituted aryl C₂₋₆ alkenyl, or optionally substituted saturated or unsaturated five- or six-membered heterocyclic group, and R¹⁷ represents a hydrogen atom.
 58. The compound according to claim 50, wherein A represents formula (IIa)

wherein (1) R¹, R², R³, and R⁴ represent a hydrogen atom, (2) R¹ and R⁴ represent a hydrogen atom, any one of R² and R³ represents a halogen atom; hydroxyl; optionally substituted C₁₋₆ alkyl; optionally substituted C₁₋₆ alkoxy; optionally substituted mono- or di-arylamino; optionally substituted mono- or di-C₁₋₆ alkylamino in which the dialkylamino together may form optionally substituted cyclic amino optionally containing 1 to 3 heteroatoms; or optionally substituted mono- or di-C₂₋₆ alkenylamino in which the di-C₂₋₆ alkenylamino group together may form optionally substituted unsaturated cyclic amino optionally containing 1 to 3 heteroatoms, and the other represents a hydrogen atom, (3) R¹ and R⁴ represent a hydrogen atom, and R² and R³, which may be the same or different, represent a halogen atom; hydroxyl; optionally substituted C₁₋₆ alkyl; or optionally substituted C₁₋₆ alkoxy, (4) R¹ and R⁴ represent a hydrogen atom, and R² and R³ together with the carbon atoms to which they are respectively attached form an unsaturated five- to seven-membered carbocyclic ring, (5) R¹ and R⁴ represent a hydrogen atom, any one of R² and R³ represents optionally substituted mono- or di-C₁₋₆ alkylamino in which the di-C₁₋₆ alkylamino together may form optionally substituted cyclic amino optionally containing 1 to 3 heteroatoms, and the other represents a hydrogen atom, or (6) R¹ and R⁴ represent a hydrogen atom, any one of R² and R³ represents optionally substituted C₁₋₆ alkoxy, and the other represents a hydrogen atom, and * represents a bond to —C(═O)—NH(—Z) R⁵ represents formula (IIIb) or formula (IIIc)

wherein (i) D, E, and J represent a carbon atom, G represents an oxygen or sulfur atom, any one or two of R⁸, R⁹, and R¹⁰, which may be the same or different, represent a halogen atom; hydroxymethyl; C₁₋₆ alkyl optionally substituted by a halogen atom; or C₁₋₆ alkoxy optionally substituted by a halogen atom, and the others represent a hydrogen atom, or (ii) D, E, and J represent a carbon atom, G represents an oxygen or sulfur atom, one of R⁸, R⁹, and R¹⁰ represents a group of formula (IV) —CH₂-Q-X1-R¹³  (IV) wherein Q represents an oxygen atom, a sulfur atom, sulfinyl, or sulfonyl, X1 represents a bond or straight chain or branched chain alkylene having 1 to 5 carbon atoms, R¹³ represents a hydrogen atom, a halogen atom, C₁₋₆ alkyl, C₁₋₆ alkoxy, C₁₋₆ alkylthio, mono- or di-C₁₋₆ alkylamino in which the di-C₁₋₆ alkylamino group may form cyclic amino optionally containing 1 to 3 heteroatoms, aryloxy, arylthio, hydroxyl, carboxyl, —S(═O)₂(—OH), C₁₋₆ alkoxy- or aryloxy-carbonyl, C₁₋₆ alkylcarbonyl, aryl, or a heterocyclic group optionally substituted by alkyl optionally substituted by mono- or di-C₁₋₆ alkylamino in which the di-C₁₋₆ alkylamino group may form cyclic amino optionally containing 1 to 3 heteroatoms, and one or two alkyl groups on the amino group and the cyclic amino moiety are optionally substituted by hydroxyl; or a group of formula (V)

wherein X2 represents a bond or straight chain or branched chain alkylene having 1 to 5 carbon atoms, X3 represents a bond or straight chain or branched chain alkylene having 1 to 5 carbon atoms, R¹⁴ and R¹⁵, which may be the same or different, represent a hydrogen atom; a halogen atom; C₁₋₆ alkyl optionally substituted by hydroxyl, a halogen atom, aryl optionally substituted by a halogen atom, C₁₋₆ alkyl, or C₁₋₆ alkyloxy, a heterocyclic group optionally substituted by a halogen atom, C₁₋₆ alkyl, or C₁₋₆ alkyloxy, and, when one or two alkyl groups on the amino group and the cyclic amino moiety are substituted by two C₁₋₆ alkyl groups, they together may form C₃₋₇ cycloalkyl; C₁₋₆ alkoxy; C₁₋₆ alkylthio; mono- or di-C₁₋₆ alkylamino in which the di-C₁₋₆ alkylamino group may form cyclic amino optionally containing 1 to 3 heteroatoms, and one or two alkyl groups on the amino group and the cyclic amino moiety are optionally substituted by hydroxyl; arylamino in which the amino group is optionally substituted by C₁₋₆ alkyl; mono- or di-C₁₋₆ alkylcarbamoylmethyl in which the di-C₁₋₆ alkylamino may form cyclic amino optionally containing 1 to 3 heteroatoms, and one or two alkyl groups on the amino group and the cyclic amino moiety are optionally substituted by hydroxyl; aryloxy; arylthio; an oxygen atom (═O); hydroxyl; carboxyl; C₁₋₆ alkoxy- or aryloxy-carbonyl; C₁₋₆ alkylcarbonyl; aryl optionally substituted by a halogen atom or hydroxyl; or a heterocyclic group, provided that, when X2 represents a bond, R¹⁴ represents a hydrogen atom, or when X3 represents a bond, R¹⁵ represents a hydrogen atom, or R¹⁴ and R¹⁵ together with a nitrogen atom to which they are respectively attached to may form a heterocyclic group that may contain 1 to 3 heteroatoms in addition to the nitrogen atom, to which R¹⁴ and R¹⁵ are attached, and is optionally substituted by hydroxyl; C₁₋₆ alkyl optionally substituted by hydroxyl, a halogen atom, aryl optionally substituted by a halogen atom, C₁₋₆ alkyl, or C₁₋₆ alkyloxy, or a heterocyclic group optionally substituted by a halogen atom, C₁₋₆ alkyl, or C₁₋₆ alkyloxy, and, when one or two alkyl groups on the amino group and the cyclic amino moiety are substituted by two C₁₋₆ alkyl groups, they together may form C₃₋₇ cycloalkyl; mono- or di-C₁₋₆ alkylamino in which the di-C₁₋₆ alkylamino may form cyclic amino optionally containing 1 to 3 heteroatoms, and one or two alkyl groups on the amino group and the cyclic amino moiety are optionally substituted by hydroxyl; a saturated or unsaturated five- or six-membered heterocyclic group; mono- or di-C₁₋₆ alkylcarbamoylmethyl in which the di-C₁₋₆ alkylamino group may form cyclic amino optionally containing 1 to 3 heteroatoms, and one or two alkyl groups on the amino group and the cyclic amino moiety are optionally substituted by hydroxyl; phenyl; or an oxygen atom (═O), and, when one carbon atom in the cyclic amino moiety is substituted by two C₁₋₆ alkoxy groups which may be the same or different, the two alkoxy groups together may form group —O—(CH₂)_(p)—O— wherein p is an integer of 2 to 4, and the cyclic amino group may condense with a monocyclic or bicyclic aromatic carbocyclic ring or a monocyclic or bicyclic aromatic heterocyclic ring to represent a bicyclic or tricyclic heterocyclic group; and the others represent a hydrogen atom, Z represents group (A), group (B), or group (C):

wherein R⁶ represents a hydrogen atom or C₁₋₆ alkyl, R⁷ represents optionally substituted aryl, optionally substituted aryl C₁₋₆ alkyl, optionally substituted aryl C₂₋₆ alkenyl, or optionally substituted saturated or unsaturated five- or six-membered heterocyclic group, and R¹⁷ represents a hydrogen atom. 59-65. (canceled)
 66. A pharmaceutical composition comprising as an active ingredient a compound according to claim 50 or a pharmaceutically acceptable salt thereof. 67-86. (canceled)
 87. A method for preventing or treating a disease for which serum phosphorus lowering action or phosphate transport inhibition is therapeutically effective, said method comprising the step of administering a therapeutically or prophylactically effective amount of a compound according to claim 50 or a pharmaceutically acceptable salt thereof to a mammal.
 88. The method according to claim 87, wherein the disease for which serum phosphorus lowering action or phosphate transport inhibition is therapeutically or prophylactically effective is hyperphosphatemia.
 89. The method according to claim 87, wherein the disease for which serum phosphorus lowering action or phosphate transport inhibition is therapeutically or prophylactically effective is renal failure or chronic renal failure.
 90. The method according to claim 87, wherein the diseases for which serum phosphorus lowering action or phosphate transport inhibition is therapeutically or prophylactically effective are secondary hyperparathyroidism and primary hyperparathyroidism and diseases related thereto. 91-96. (canceled) 